Метка: Toxicological profile
Токсикологический профиль консервантов / Toxicological profile of preservatives
METHYLCHLOROISOTHIAZOLINONE, METHYLISOTHIAZOLINONE:
| [SCCS/1238/09]: Acute oral toxicity: male LD50 > 5000 mg/kg bw (> 75 mg a.i./kg bw) female LD50 3310 mg/kg bw (~ 49.6 mg a.i./kg bw). Acute dermal toxicity: Male & female LD50 1008 mg/kg bw (141 a.i. mg/kg bw) Acute inhalation toxicity: Male & female 4hr aerosol exposure LC50 2.36 mg/L air, confidence limits of 1.60 to 4.82 and a slope of 2.2. (LC50 0.33 mg a.i./L, confidence limits of 0.22 to 0.67, and a slope of 2.2. Irritation and corrosivity: P56, (5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in a ratio of 3:1) is corrosive or irritating at high concentrations. No adequate data is given to support safe use at a maximum authorised concentration of 0.0015 % in rinse-off cosmetic products. Nevertheless, the weight of evidences over several decades of consumer exposure to cosmetic products indicates that skin and/or mucous membrane irritation is not a problem under the conditions of use in leave-on and rinse-off products. Skin sensitization: More recent investigations by Basketter et al., (2005) evaluated the LLNA and have shown that EC3 values of a number of allergens, including CMI/MI compare well with human data such as human predictive assays (HRIPT). The data demonstrates that CMI/MI is an extreme sensitiser in animals. Dermal / percutaneous absorption: 14C-RH-886T was applied to the intact and abraded skin of rabbits over a 3 day period. No radioactivity was found in the blood at any time point. Following dermal application (24 hr exposure) of CMI or MI, approximately 15 and 24% of the dose, respectively, was systemically available. Within 72 to 96 hr most of the absorbed radioactivity was excreted (predominantly in the urine). Sub-chronic (90 days) oral / dermal / inhalation toxicity: No systemic toxicity was observed up to and including the highest dose of either CMI/MI (800 ppm, equivalent 29.1 mg a.i./kg/day] or its metabolites, N-methyl malonamic acid and malonic acid tested in combination [13 to 15 mg/kg/day N-methyl malonamic acid/2.6 to 3.0 mg/kg/day malonic acid]. The No Observed Effect Level (NOEL) in this study was estimated to be greater than or equal to the highest dose tested (29.1 mg a.i. /kg/day). The No Observed Effect Level (NOEL) was 0.34 mg/m³, based on minimal irritation of the respiratory tract at 1.15 mg/m³. No adverse effects on the histopathology of any tissues/organs distant from the site of dosing were noted up to and including the highest dose tested (2.64 mg a.i./m³). The value of the acute, subchronic and reproductive toxicity studies is limited as the test formulations are not properly characterised and there are other data gaps. For the calculation of the Margin of Safety, the parental P1 NOAEL of 2.8 mg a.i./kg bw/day from the Kathon MW two generation reproductive toxicity study was used. Mutagenicity and Carcinogenicity: CMI/MI was not considered to be carcinogenic, since there was no increase in the type or incidence of tumours. CMI on its own was positive in vitro in a gene mutation test in bacteria without S9-mix only. However, a DNA binding study in vivo was negative indicating that the possibility that CMI alone has genotoxic potential in vivo is low. Both MI and NMMA were negative under in vitro conditions and consequently not tested in vivo. |
BENZALKONIUM CHLORIDE:
| [SCCNFP/0539/01 and SCCNFP/0762/03]: Acute oral toxicity: — Oral, Rat, LD50 = 420 mg/kg — Oral, rat, LD50 = 295 mg/kg (95% conf. limits: 160 and 543 mg/kg) — I. P., Rat, LD50 = 33 mg/kg — I.V., Rat, LD50 = 19 mg/kg. Repeated dose oral toxicity: A supplementary 28-day study in rats with the same feeding levels was conducted to verify and extend certain findings in the previous study. The results confirmed most of the changes seen at the top dose, including caecal enlargement. The latter finding was not accompanied by histopathological changes. Decreased levels of serum-P seen at the two higher levels in the previous study did not occur in the present study. Therefore, 500 ppm (or 40 mg/kg bw) was the NOAEL in the supplementary study. Repeated dose dermal toxicity: The skin lesions were more or less similar to those observed in rats. The no systemic effect level was then at least 50 mg/kg bw/day. Chronic toxicity: A two-year study has been conducted with groups of 5 rats/sex, fed diets containing 0, 50, 200, 1000, 2500 or 5000 ppm (providing 0, 4, 16, 80, 200 or 400 mg/kg bw/day). The top dose induced mortality. With 2500 and 5000 ppm testicular atrophy and caecal enlargement occurred. With 1000 ppm there was only caecal enlargement. The NOAEL can be considered at least 80 mg/kg bw. Irritation & corrosivity: Three of the five subjects exhibited responses to the 5%, 2.5%, 1.25% and/or the 0.63% level. No reactions were observed with the 0.31% concentration and this was considered an appropriate level for a subsequent repeated insult patch test. The test was performed on New Zealand White rabbits according to OECD Guideline n° 405 (3 rabbits). A 0.1 % aqueous solution of benzethonium chloride was minimally irritant to the rabbit eye without rinsing after instillation of the solution. Sensitisation: During the induction phase, six subjects showed mild to well-defined erythema and one subject exhibited mild to marked responses. With one exception (the subject that showed marked responses during induction) all observations were negative during the challenge phase. (The one responding subject was classified as a ‘reactive individual’ and his data were not considered in the final results). It was concluded that benzethonium chloride when administered at 0.3% did not elicit dermal irritation and/or sensitisation. Toxicokinetics (incl. Percutaneous absorption): The in vitro percutaneous absorption of [14C]-Benzethonium Chloride through human skin 1.0% (w/v) solution in ethanol. The in vitro percutaneous absorption of [14C]-Benzethonium Chloride through human skin 0.1% (w/v) in GMS-cream and ethanol. Mutagenicity: An Ames test with S. typhimurium strains TA98, TA100, TA 1535, TA 1537 was negative in the absence (0.01 to 1.0 μg benzethonium chloride/plate) or presence (1.0 to 100.0 μg benzethonium chloride/plate) of metabolic activation. Activation was brought about by the addition of S9 mix from male rat liver induced by „Aroclor 1254“. Carcinogenicity: Under the conditions of this dermal carcinogenicity study there was no evidence of carcinogenic activity of benzethonium chloride in male or female B6C3F1 mice up to the highest dose applied, 1.5 mg/kg bw/day. |
DIAZOLIDINYL UREA:
| [SAFETY DATA SHEET. PRESERVATIVE GPL]: Acute toxicity: LD50 > 2000. Skin Corrosion/Irritation: Non-irritating to rabbit (5 % aqueous solution) and guinea pig skin (100 % wettable powder). Serious eye damage/irritation: Non-irritating to rabbit eye (1 & 5 % aqueous solutions). Respiratory or skin sensitization: Non-sensitizing to guinea pigs (0.1 % aqueous solution). Germ cell mutagenicity: Non-mutagenic (Ames assay). Toxicokinetics: Nonteratogenic in rats receiving dermally 30 — 300 mg/kg/day from days 6 — 15 of gestation. Phototoxicity: Non-phototoxic (0.5 %). Subchronic Oral Toxicity: Rat 90; 10, 25, 100 mg/kg/day — no observed adverse effect level (NOAEL) 100 mg/kg/day. 28 day; 100, 300, 900 mg/kg. no observed adverse effect level (NOAEL) 100 mg/kg/day |
SODIUM BENZOATE:
| [SCCNFP/0532/01, final OPINION of the scientific committee on cosmetic products and non-food products intended for consumers concerning benzoic acid and sodium benzoate adopted by the SCCNFP during the 20th plenary meeting of 4 June 2002] Acute toxicity: Oral LD50 in rats is between 2 100 and 4 070 mg/kg bw as acid. Corrosivity and irritation: Not a skin irritant. Slightly irritating to rabbit eye in 100 % concentration. Skin sensitization: Benzoic acid not sensitising in mouse ear swelling test [CIR Amended Final Safety Assessment Benzyl Alcohol, and Benzoic Acid and its Salts and Benzyl Ester October 17, 2011]. [CIR Amended Final Safety Assessment Benzyl Alcohol, and Benzoic Acid and its Salts and Benzyl Ester October 17, 2011]:Repeated toxicity: From a 90-day study in rats a NOAEL of 1 300 mg/kg bw for males and females respectively could be established. Mutagenicity/Genotoxicity: No evidence of mutagenic or genotoxic activity for benzoic acid. For sodium benzoate not mutagenic in Ames tests but some positive results occur in in vitro chromosome aberration tests and it cannot be ruled out that sodium benzoate is genotoxic in vitro. Carcinogenicity: No carcinogenic effects from sodium benzoate in rat and mouse studies. Reproductive toxicity: In a 4-generation reproduction toxicity test in rats with benzoic acid given by gavage, the NOAEL for all endpoints was 500 mg/kg bw/day. Phototoxicity: Benzoic acid absorbs UV light below 300 nm. Benzyl benzoate produced no photoirritation or phototoxicity after 3 irradiations, a slight phototoxicity after 4 irradiations. |
SODIUM DEHYDROACETATE:
| [MSDS, Lactokine™ Fluid PF]: Acute oral toxicity: LD50 (oral, rat) > 2000 mg/kg (not toxic); Primary irritation to the skin (rabbit): not irritant; Irritation to eyes (rabbit): minimal irritant; Sensitisation (In case of skin contact): Not sensitizing. [CIR. Final Report on the Safety Assessment of Sodium Dehydroacetate and Dehydroacetic Acid]:LD50(oral, mouse) = 1050 mg/kg; LD50(dermal, rabbits) = 2000 mg/kg (nontoxic). Primary skin irritation studies conducted on rabbits showed that compounds to be practically nonirritating. Sodium Dehydroacetate was found to exhibit minimal eye irritation, whereas cosmetic products containing up to 0.2 percent Sodium Dehydroacetate were nonirritating. Sodium Dehydroacetate was found practically nonirritating, nonsensitizing, nonphotosensitizing, and nonphototoxic in numerous clinical tests. No evidence of mutagenicity was found in numerous studies on Sodium Dehydroacetate. [Survey and health and environmental assessment of preservatives in cosmetic products / The Danish Environmental Protection Agency, 2015]:NOAEL (for dehydroacetic acid, oral, rat 2-year study) = 100 mg/kg bw/day. |
POTASSIUM SORBATE:
[Regulation (EU) No 528/2012 concerning the making available on the market and use of biocidal products. Evaluation of active substances. Assessment Report. Potassium sorbate. February 2015]: Acute toxicity: Potassium sorbate is not acutely toxic or harmful when administered orally (LD50 > 10000 mg/kg bw) or dermally (LD50 > 2000 mg/kg bw). Medium – term toxicity: No substance – related adverse effects could be observed in the repeated oral administration tests in rats and dogs. Oral short-term NOAEL (rats) = 7000 mg/kg bw (the highest dose tested). Oral short-term NOAEL (dogs) = 1000 mg/kg bw (the highest dose tested). Genotoxicity: Potassium sorbate did not display a genotoxic potential either in vitro or in vivo. Chronic toxicity/ Carcinogenicity: Oral NOAEL (24-mo. study, rat) = 750 mg/kg bw/d, based on reduced body weight (gain), increased organ weights (liver, kidney, thyroid) and focal fatty changes in livers of female animals at 5000 mg/kg bw/d. Oral NOAEL (18-mo. study, mouse) = 1400 mg/kg bw/d, based on reduced terminal body weight and increased organ weights (liver, kidney) at 7000 mg/kg bw/d. No evidence was found for a carcinogenic potential of potassium sorbate. Taking into account the large dose spacing used in the 24-month rat study as well as the marginal nature of the effects observed at the high-dose level, it was decided that the limit dose level of 1000 mg/kg bw/d which proved safe in the 90-d study in dogs. Reproductive and developmental toxicity: The teratogenicity studies did not indicate any specific embryo/foetotoxic potential of potassium sorbate. Foetal growth retardation and embryo-foetal death and/or reduced viability were present in rabbits at a dose of 1000 mg/kg bw/d, which also induced slight maternal toxicity (increased respiration rate, decreased food consumption and body weight gain, coarse spleen surface). A dose of 3000 mg/kg bw/d resulted in maternal lethality and increased morphologic abnormalities (brain, limbs) in the foetuses of surviving dose. The following NOAELs were established from the developmental studies: Rats: NOAEL (maternal toxicity/embryotoxicity, teratogenicity) = 340 mg/kg bw/d (the highest dose testes); Rabbits: NOAEL (maternal toxicity) = 300 mg/kg bw/d, based on reduced food consumption and body weight gain, clinical signs, coarse spleen surface, mortality, abortions at 1000 mg/kg bw/d; NOAEL (embryotoxicity) = 300 mg/kg bw/d, based on decreased body weight, fetal survival, embryo lethality, and morphological abnormalities at 1000 mg/kg bw/d; NOAEL (teratogenicity) = 1000 mg/kg bw/d (the highest dose tested). NOAEL (parental and reproductive toxicity): 3000 mg/kg bw/d (the highest dose tested); NOAEL (offspring toxicity): 1000 mg/kg bw/d reduced postnatal body weight gain, development, and behaviour at 3000 mg/kg bw/d. |
BENZYL ALCOHOL:
| [MSDS, EUXYL K700]: Acute oral toxicity: LD50 (Rat): 1.620 mg/kg Acute inhalation toxicity: LC50 (Rat): 4,2 mg/l, 4 h, dust/mist, OECD Test Guideline 403 Skin corrosion/irritation Rabbit, OECD Test Guideline 404, No skin irritation Serious eye damage/eye irritation Rabbit, OECD Test Guideline 405, Moderate eye irritation Respiratory or skin sensitisation Does not cause skin sensitisation.Guinea pig Repeated dose toxicity Rat, NOAEL: 400 mg/kg, Oral [Final Report on the Safety Assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate / International Journal of Toxicologa, 20 (Suppl.3): 23-50, 2001]:Dased on the available data, the CIR Expert Panel concludes that Benzyl Alcohol, <…> are safe for use in cosmetic formulations at concentrations up to 5 %. |
SALICYLIC ACID:
| [CIR. Amended Safety Assessment of Salicylic Acid and Salicylates as Used in Cosmetics]: Acute Toxicity Studies (Oral): A single dose of an aqueous solution of Salicylic Acid (in gum Arabic) was administered to 10 Wistar rats. LD50 values in the range of 0.5 to 2 g/kg were reported. Acute Toxicity Studies (Dermal): In a study involving 3 New Zealand White rabbits, Salicylic Acid (0.5 g, moistened with 0.5 ml water) was applied, under a semi-occlusive patch, for 4 h to a 6.25 cm2 area of skin. 4 The animals were observed for up to 14 days after application. None of the animals died, and there were no clinical signs of systemic toxicity during the study. Subchronic Toxicity Studies: Two 91-day studies involving New Zealand White rabbits (number of animals used per study not stated) were performed to evaluate the cutaneous and systemic toxicity of 2 cleansing formulations containing 0.5 % Salicylic Acid.5 The undiluted product or the product diluted to a concentration of 50 % w/v in distilled water (effective Salicylic Acid concentration = 0.25 %) was applied. The test article (dose volume of 2 ml/kg; dose = 10 mg/kg) was applied (method not stated) to intact skin 5 times per week (7 h per day). Control rabbits were treated with distilled water. Both gross and histopathological examinations were performed. None of the animals died, and there were no statistically significant differences in mean body weight or organ weights during the study. Clinical evaluations as well as clinical chemistry, hematology, and histopathological examinations provided no evidence of systemic toxicity. Developmental and reproductive toxicity studies: Groups of 20 gravid Wistar rats were fed a diet containing 0.06 %, 0.1 %, 0.2 %, or 0.4 % Salicylic Acid on gestation days 8 to 14.1 Significant reproductive effects were observed in the 0.4 % dietary group, and skeletal anomalies were observed in the 0.2 % group. Only one dam gave birth to live neonates in the 0.4 % dietary group, and skeletal anomalies were observed in 0.2 % neonates. Groups of Wistar rats were dosed orally with Salicylic Acid at a dose of 75, 150, or 300 mg/kg on gestation days 8-14. Fetal mortality was 26 % and 100 % in the 150- and 300-mg/kg groups. Significant reproductive effects were observed in fetuses and neonates of the 150 mg/kg group. Groups of 10 Sprague-Dawley rats were dosed twice daily with 10 mg/kg Salicylic Acid on gestation days 20 and 21, and the mean gestation period was increased. Photocarcinogenicity: The mouse lymphoma assay (L5178Y mouse lymphoma cells) was used to evaluate the genotoxicity of Salicylic Acid (in deionized water) with and without metabolic activation. Doses up to 1400 μg/ml were tested. Cyclophosphamide and methylmethanesulfonate served as positive controls. Salicylic acid was not genotoxic, with or without metabolic activation, at any of the doses tested. Photocarcinogenicity In a National Toxicology Program (NTP) photocarcinogenicity study, the effects of synthetic solar light on the skin of hairless mice that had been treated with creams containing Salicylic Acid were evaluated.60 Creams containing Salicylic Acid (0 %, 2 %, or 4 %), were applied to the skin of groups of 18 male and 18 female hairless mice in the mornings. Additional groups of 36 male and 36 female mice were not exposed to the cream. In the afternoons, groups of animals were exposed to one of three strengths of synthetic solar light for 4 h. Other groups were not exposed to light and were control groups. The treatment and exposures were performed five days per week for 40 weeks, during which time the animals were monitored for the development of skin cancers. Greater strengths of light increased the incidences of skin cancers in mice not given a cream or given a cream with no acid included. Creams containing Salicylic Acid decreased the incidence of skin tumors in mice receiving the lower of the two light intensities. It was concluded that Salicylic Acid had some protective effect against photocarcinogenicity at lower intensities. |
SODIUM BICARBONATE:
| [CIR. Safety Assessment of Simple Carbonate Salts as Used in Cosmetics]: Acute Toxicity Studies (oral): LD50 = 8.9 g/kg (fed rats), 7.57 g/kg (fasted rats on wire floored cages), and 8.46 g/kg (fasted rats bedded on wood shavings). Subchronic Oral Toxicity: Ten White Leghorn chicks (15 days old) were given 0.5 % Sodium Bicarbonate in drinking water for 75 days. (60) The 10 control chicks received unsupplemented feed and water. Blood samples from both groups were drawn every 15 days, and pooled samples were used for biochemical analyses. A gradual rise in total protein (TP), uric aicd (UA), and nonprotein nitrogen (NPN) in the serum was reported for Sodium Bicarbonate-fed chicks. The increase in TP was statistically significant on the 45th day of feeding, whereas UA and NPN increased significantly on the 15th day. The authors noted excessive watery droppings following Sodium Bicarbonate administration as the possible cause of dehydration and the concentration of serum proteins. Significantly high UA values were attributed possibly to nephrotoxic effects of Sodium Bicarbonate, which led to decreased excretion of UA. Significantly high NPN values were attributed to hyperuric acidemia. Ocular Irritation: the test substance could not be classified as an ocular irritant. Skin Irritation: It was concluded that the test substance was not a primary irritant. Teratogenicity: Sodium Bicarbonate did not induce teratogenic effects when administered orally at the following doses: 580 mg/kg (mice), 340 mg/kg (rats), and 330 mg/kg (rabbits). Mutagenicity: Sodium Bicarbonate was not mutagenic to Saccharomyces cerevisiae strain D4 and Salmonella typhimurium strains TA1535, TA1537, and TA1538 in suspension and plate tests, both in the presence and absence of metabolic activation. [SAFETY DATA SHEET. BICAR® Sodium Bicarbonate Ultra Fine Grade. SOLVAY CHEMICALS, INC.]:Rat , female Application Route: Oral NOAEL teratogenicity: > 340 mg/kg Method: according to a standardized method Highest dose tested The product is not considered to be embryotoxic/fetotoxic. Rabbit , female Application Route: Oral NOAEL teratogenicity: > 330 mg/kg Method: according to a standardized method Highest dose tested The product is not considered to be embryotoxic/fetotoxic. |
SODIUM METABISULFITE:
| [SCCNFP/0648/03, final] Acute Oral Toxicity: The acute oral LD50 was 1131 and 1903 mg/kg for female and male rats, respectively (Eastman Kodak Co. 1980). Corrosivity and irritation: Sodium metabisulfite was found to be severe eye irritants when tested neat and eye contact should be avoided. Carcinogenicity: Sodium metabisulfite was tested for carcinogenicity in one study in rats by oral administration. The incidences of thyroid and pituitary tumours were increased in treated males, but no dose–response relationship was observed. Mutagenicity/Genotoxicity: Sodium metabisulfite was not found to be genotoxic in the test battery. None of the in vivo tests have shown a genotoxic potential. Reproductive and developmental toxicity: Sodium Bisulfitewas not teratogenic for mice, rats, hamsters, or rabbits at doses of 150, 110, 120, and 100 mg/kg, respectively (Food and Drug Research Labs 1972a, 1974a). Sodium Metabisulfite Sodium Metabisulfitewas not teratogenic for mice, rats, hamsters, or rabbits at doses of 160, 110, 120, and 123 mg/kg, respectively (Food and Drug Research Labs 1972b, 1974b). NOAEL = 72 mg/kg/day (expressed as sulfur dioxide). |
SODIUM METHYLPARABEN:
| [Information on Registered Substances of ECHA]: Acute toxicity: LD50 (oral, rat) > 5 000 mg/kg bw. Skin irritation / corrosion: (in vitro) irritating (H315). Eye irritation: (in vivo) corrosive (H318). *The available data on skin irritation and eye irritation of the test substance meet the criteria for classification as Skin Irritant (H315) and Irreversible effects on the eye (H318) according to Regulation (EC) 1272/2008. Skin sensitization: no adverse effect observed (not sensitising). Carcinogenicity: No significant carcinogenic effects observed. Repeated dose toxicity: Based on the results of this study (of a 28 day oral toxicity), the no-observed-adverse-effect-level (NOAEL) for the test item, Methylparaben, was considered to be 250 mg/kg body/day. |
PHENOXYETHANOL:
| [SCCS (Scientific Committee on Consumer Safety), Opinion on Phenoxyethanol, 16 March 2016, SCCS/1575/16] Acute toxicity: The rat oral LD50 values in females and males were determined to be 1840 mg/kg bw and 4070 mg/kg bw, respectively. Corrosivity and irritation: Mild skin irritant; eye irritating in 100 % concentration. Skin sensitization: Not a skin sensitiser (OECD 406). Repeated toxicity: From an oral 90 – day study in rats NOAEL is considered to be 5000 ppm corresponding to 369 mg/kg/day in males and 652 mg/kg/day in females based on effects on red blood cell parameters and the histopathological changes in the kidney and urinary bladder which occurred at doses ≥ 10,000 ppm. Based on the lack of treatment-related effects on body weight, organ weights, haematological and clinical chemistries and gross and histopathological examinations in a dermal 90-day study in rabbits, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was concluded to be 500 mg/kg bw/day under the conditions of this study. To account for the dosing schedule used in this study, the NOAEL should be multiplied by a factor of 5/7 to give an adjusted NOAEL of 357 mg/kg bw/day. Mutagenicity/Genotoxicity: Not mutagenic or genotoxic. Carcinogenicity: Not carcinogenic in rat and mouse studies. Reproductive toxicity: From a 2-generation study in mice it can be concluded that fertility was only minimally affected at the highest dose, but evidence of significant toxicity to the offspring was observed when 2-phenoxyethanol was administered at the mid- and high-dose level. For males, a NOAEL of 400 mg/kg bw/day was calculated. For females, the NOAEL was approximately 950 mg/kg bw/day. Not a developmental toxicant. Toxicokinetic: Data in rats suggest higher systemic availability of 2-phenoxyethanol after dermal exposure than after oral exposure. In humans single oral exposure of phenoxyethanol results in rapid first pass metabolism in the liver why oral exposure is not considered relevant to dermal exposure. Phototoxicity: No experimental data available but human epidemiological data do not suggest that phenoxyethanol is phototoxic or photo allergenic. |
METHYLPARABEN, ETHYLPARABEN, PROPYLPARABEN, BUTYLPARABEN
Acute toxicity: Low acute toxicity has been identified in the OECD TG 401 studies on the acute oral toxicity of methyl-, ethyl- and propylparaben in different rodent species (mice, rats, dogs and guinea pigs) after oral administration. LD50 values lie between 2000 and 8000 mg/kg bw. For other routes such as subcutaneous and intraperitoneal administration, the LD50 values are around 10 times lower [RIVM Report 2017-0028]. [Safety Assessment of Parabens as Used in Cosmetics. CIR. May 19, 2017]: Irritation: A primary eye irritation study in humans showed methylparaben to be nonirritating at concentrations up to 0.3 %. When tested on human skin, each of the parabens began producing evidence of irritation only when concentrations exceeded 5 to 12 percent. Considering the order of magnitude of these concentrations, it may be concluded that the parabens are relatively nonirritating at the concentrations used in cosmetic products. Some individuals, however, may develop allergic reactions to parabens Developmental and reproductive toxicity (dart) studies: Parabens have been extensively studied to evaluate male reproductive toxicity. In one in vitro study, sperm viability was eliminated by concentrations as low as 6 mg/ml Methylparaben, 8 mg/ml Ethylparaben, 3 mg/ml Propylparaben, or 1 mg/ml Butylparaben, but an in vivo study of 0.1 % or 1.0 % Methylparaben or Ethylparaben in the diet of mice reported no spermatotoxic effects. Estrogenic activity of parabens and PHBA was increased in human breast cancer cells in vitro, but the increases were around 4 orders of magnitude less than that of estradiol. Several overviews of the endocrine disruption (estrogenic and androgenic effects) generally note that any effect of parabens is weak. Another assessment of the endocrine disrupting/estrogenic potential of parabens noted that parabens do not have genotoxic, carcinogenic, or teratogenic potential and are rapidly hydrolyzed to p-hydroxybenzoic acid and excreted. [RIVM Report 2017-0028]:Genotoxicity/carcinogenicity: Based on the weight of evidence from the available in vitro and in vivo genotoxicity studies, methylparaben is not considered to be genotoxic. Some in vitro genotoxicity tests indicated weakly positive results, but all in vivo tests were negative. Ethyl- and propylparaben did not induce statistically significant increases in the in vitro or in vivo assays for genotoxicity. From the available in vivo carcinogenicity studies on methyl-, ethyl- and propylparaben it can be concluded that they are not considered to be carcinogenic. [Safety Assessment of Parabens as Used in Cosmetics. CIR. May 19, 2017]: Subchronic and chronic toxicity tests: A number of acute, subchronic, and chronic toxicity tests have been performed on the parabens using a wide variety of routes of administration. From these data, it is readily apparent that these ingredients exhibit a very low order of toxicity and must certainly be considered safe in this respect for cosmetic use in the usual quantities employed as a preservative. [RIVM Report 2017-0028]:TGs are currently lacking for methyl- and ethylparaben. A No Observed Adverse Effect Level (NOAEL) of 1000 mg/kg bw/day has been derived by the Scientific Committee on Consumer Safety (SCCS) and the European Food Safety Authority (EFSA) for methyl- and ethylparaben based on the absence of reproductive effects up to that dose in repeated dose toxicity studies. [SCCS/1514/13]:NOAEL (for all parabens) is 1000 mg/kg bw/day. |