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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Read Across Justification for Ethyl Acrylate Reproductive and Developmental Toxicity

The principle of toxicological read-across within the lower alkyl acrylate esters category, and for this analogue read across, is that the acrylates with the common chemical reactivity and common primary metabolic pathway to acrylic acid have similar toxicological properties. These aspects can be either qualitatively categorised as “same type of effect” (i.e. scenario 4 according to RAAF (ECHA, 2017); chemical reactivity of the category members) or as “(Bio) transformation to common compound(s)” (i.e. scenario 3 according to RAAF; common primary metabolic pathway). Read-across between Ethyl acrylate and Methyl acrylate or n-Butyl acrylate is supported by the similarity among these acrylates regarding toxicokinetics and toxicodynamics behaviour.The key read-across hypothesis that supporting this approach is that these acrylate esters are rapidly metabolised via two pathways: esterase hydrolysis to acrylic acid and alcohols and glutathione conjugation, hence they have similar toxicological properties (i.e. a lack of systemic toxicity).Overall, the uncertainties associated with the read-across, based on prediction of systemic toxicity of these acrylate esters, are considered to be minimal. The alcohol metabolites of acrylate esters are not expected to make a significant contribution to the systemic toxicity profiles of these acrylate esters due to local toxicity limiting the dose that can be applied.

Read-across from the studies on the source substances are considered to be an appropriate adaptation to the standard information requirements of Annex X of the REACH Regulation for the target substances, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.The justification of the proposed read-across approach is elaborated in the next sections.The endpoint specific “scientific assessment option” of the read across is “acceptable with high/medium confidence”.

Physico-Chemical Properties

In RAAF nomenclature, the read-across approach for this endpoint is described in scenario 4 (different compounds have qualitatively similar properties) and governed by AE 4.3 (common underlying mechanism, quantitative aspects).Here, a clear trend of increasing viscosity with increasing molecular weight and chain length is observed.Read-across is applied with a high level of certainty.

In the toxicokinetic section of the CSR (Section 5), as well as in the attached Acrylate Category Justification Report, the similarity of the Acrylates in the metabolism was justified (scenario 3). For all Category members the phys-chem- and environmental fate data are available which show similarity or a similar trend depending on the length and the branching of the side chain for the Acrylates. Additionally it can be shown that these acrylates have qualitatively similar properties. For most endpoints, for all members of the Category study, results are available (e.g. acute oral, acute inhalation, acute dermal, skin irritation, eye irritation, Ames test, algae and acute fish). Also, those anchor points show similarity or a similar trend depending on the length and the branching of the side chain for the Acrylates.

Toxicokinetics

As evidenced in the recentin vitrohydrolysis assays, EA has a similarly short half-life compared to MA and n-BA in rat blood (all < 2.4 min) and liver microsomes (all < 6 min). Glutathione depletion levels in the rat forestomach, in vitro conjugation, and DPRA peptide depletion were very similar (ARTF, 2017e; ARTF, 2018). The findings from the hydrolysis assays suggest that the difference in the side chain length in the acrylate esters would have no significant consequence on the hydrolysis rate or GSH conjugation.

These acrylate esters are considered to be highly similar regardingin silicotoxicodynamics. The structural alerts using the QSAR Toolbox showed a similarity in protein binding reactivity (Michael addition) with a low level of toxicity indicated by the assignment of Cramer Class I. None of these substances, including AA, are flagged as potential receptor binders. 

Repeated dose toxicity

The repeated dose toxicity studies indicate that the systemic toxicity of these acrylates is manifested mainly as reduction in bodyweight gain. Overall, the systemic toxicity for EA, MA, and n-BA is considered to be minimal. The irritancy is confirmed in the repeated dose toxicity studies with localised irritation at the site of contact following oral and inhalation administration of EA. In the oral gavage 2-year carcinogenicity studies, EA induced marked local irritation and cellular proliferation which led to forestomach tumours at high concentrations in rats and mice. In 90-day and two-year inhalation studies in rats with nBA, the observed effects were primarily irritation of eyes and nasal mucosa and mortality associated with irritation of the respiratory tract, reduced bodyweight gain and changes in clinical chemistry parameters. In addition to the reduction in bodyweight gain, organ weight changes were also noted, and the severity of nasal mucosa effects increased in a concentration-dependent manner in the two-year study. Localised irritation at the site of contact and minimal systemic toxicity were also observed in the repeated dose toxicity studies with MA and the common metabolite AA.

Due to the similarity in the toxicity profiles across the acrylate category and for the corresponding alcohols, together with the rapid metabolism rates observed in the comparative hydrolysis assay and GSH conjugation, the uncertainties associated with the read-across based prediction of reproductive toxicity of EA are considered to be minimal.

 

Reproductive toxicity

In RAAF nomenclature, the read-across approach for reproductive toxicity is described in scenario 3 “(Bio) transformation to common compound(s)”, whereas AA is the toxicologically relevant metabolite for local and systemic effects.For this endpoint, the common primary metabolic pathway of the acrylate members (i.e. common functional groups and rapid metabolism by ester cleavage leading to the common metabolite AA) is considered as the most relevant aspect of the category approach. The variable part of the read across approach is the length or configuration of the side chain of the parent ester and the alcohol metabolite and their impacts on physico-chemical properties and subsequent properties. Despite the variation, the available data support a lack of toxicity for reproduction for the respective substances across the tested species. Overall,the read-across is applied with a high level of confidence.

Methyl and n-Butyl acrylate as well as the common metabolite, acrylic acid, have been tested in reproductive toxicity studies conducted according to established study designs. Overall, the available systemic toxicity studies for these substances indicate no concerns for reproductive and developmental toxicity. A lack of intrinsic reproductive and developmental toxicity is commonly observed for all category members in the rat, mouse and rabbit.

There are no reproductive and developmental toxicity concerns for the alcohol metabolites of EA, MA, or n-BA that are relevant for human (ethanol, methanol, and n-butanol, respectively). No fertility or developmental effects of ethanol were seen at inhalation exposures up to 16000 ppm (30,400 mg/m3) with the lowest reported NOAEL for fertility by the oral route of 2000 mg/kg bw in rats, equivalent to a blood alcohol concentration of 1320 mg/L. Most of the available studies use very high doses and few are individually robust enough to allow a NOAEL to be established. However, the collective weight of evidence is that the NOAEL for the developmental effects in animals is high, typically ≥ 6400mg/kg bw, which is much higher dose level compared to the maternally toxic dose level of 3600 mg/kg bw (OECD, 2004b). Methanol exhibits some reproductive and developmental effects depending on the tested species. Teratogenic effects are observed in the rodent studies. However, based on major species differences between humans and rodents (i.e. metabolic pathway/enzymes, mode of action, toxicokinetics), the overall weight of evidence along with the evaluation of reproductive toxicity provided by the Committee for Risk Assessment published in 2014 concluded that methanol does not appear to be toxic to reproduction (ECHA, 2019). There are no reproductive and developmental toxicity concerns for n-butanol. Based on the available rat studies, n-butanol is concluded not to be a reproductive toxicant (OECD, 2004a); n-butanol produced only mild foetotoxicity and developmental alterations at or near the maternally toxic (even lethal) dose of 8000 ppm (24000 mg/m³) throughout gestation. Overall, a lack of toxicity for reproduction for ethanol, methanol, and butanol suggests that any unknown reproductive and developmental toxicity of EA from the read-across approach for this endpoint is considered negligible.

Reproduction (fertility)

There are no one-, two-generation, or EOGRTS studies available for ethyl acrylate. However, a lack of reproductive concern was demonstrated in90-day repeated dose oral toxicity and 27-month inhalation toxicity studies in rats. No treatment-related changes were observed for the testes weights as well as the gross and microscopic pathology for testes, seminal vesicles, ovaries, and uteri up to the highest dose level tested (100 mg/kg/day or 0.92 mg/L, respectively).

There is a data gap for reproductive toxicity for EA for the oral route, and read-across to the structural analogues, Methyl and n-Butyl acrylate, is applied to predict its reproductive toxicity properties.

Ethyl acrylate

Data on reproductive organ toxicity (testes weights as well as information on gross and microscopic pathology for testes, prostate, ovaries, and uteri) were derived from a 3-month study by the oral route (EA, 5 days/week by gavage, 10 animals/sex/dose level) with Fischer rats according to the NTP protocol which is similar to OECD guideline 408. Respective results from animals exposed to the highest dose level of (110 mg/kg bw/day) did not give evidence for any impairment of the investigated reproductive organs of both sexes. 

 

Additionally, data on reproductive organ toxicity (testes weights as well as information on gross and microscopic pathology for testes, prostate, ovaries, and uteri) from a 27 month inhalation study (EA, 6 hours/day; 5 days/week, 115 animals/sex/dose level) with Fischer rats were taken into account. No histological changes were observed in the reproductive organs at any dose level. 

Methyl acrylate

In a two-generation study according to OECD TG 416 groups of 27 male and female Crl:CD(SD) rats were whole-body exposed to methyl acrylate vapours at target concentrations of 0, 5, 25, and 75 ppm for six hours/day, seven days/week, resulting in actual average concentrations of 0, 5.3 ± 0.2, 25.7 ± 0.3, and 75.4 ± 0.6 ppm, respectively (corresponding to approx. 0, 0.019, 0.092, and 0.269 mg/L).Rats were exposed daily for approximately ten weeks prior to breeding, and continuing through breeding, gestation and lactation for two generations. Maternal rats were not exposed after GD 20 through LD 4 in order to allow for parturition and initiation of lactation. Exposure of maternal rats continued from LD 5 – LD 28. In-life parameters included clinical observations, feed consumption, body weights, estrous cyclicity, reproductive performance, pup survival, pup body weights, and puberty onset. In addition, post-mortem evaluations included gross pathology, histopathology, organ weights, oocyte quantitation and sperm count, motility and morphology in adults, and gross pathology and organ weights in weanlings (BAMM 2009). 

 

Treatment-related effects in parental rats exposed to 75 ppm included decreased body weight and feed consumption in males and females throughout most of the two generation study. There were no effects on body weight or feed consumption at 25 or 5 ppm. Treatment-related, adverse histopathologic effects were present in the nasal tissues of P1 and P2 males and females exposed to 25 or 75 ppm. The incidence and severity of the nasal effects were concentration dependent. Degeneration with regeneration of the olfactory epithelium (very slight to moderate) occurred in all P1 and P2 males and females exposed to 75 ppm. Very slight olfactory epithelial degeneration, without accompanying regenerative hyperplasia, was noted in some of the P1 and P2 females and P2 males exposed to 25 ppm. There were several histopathologic effects that accompanied the degeneration of the olfactory epithelium. Very slight or slight degeneration of the olfactory nerve was present in most of the P1 and P2 males and females exposed to 75 ppm, and one P1 male exposed to 25 ppm. Very slight or slight chronic-active inflammation was present in 16/27 P1 males, 20/27 P1 females, 14/27 P2 males, and 8/27 P2 females exposed to 75 ppm, and in one or two males and females from both generations exposed to 25 ppm. Very slight necrosis of individual olfactory epithelial cells was present in most of the P1 and P2 males and females exposed to 75 ppm, and a few P1 and P2 animals (one to four per sex) exposed to 25 ppm. Very slight mineralization of the olfactory epithelium was present in one or two P1 and P2 animals exposed to 25 ppm, and in 6/27 P1 males, 4/27 P1 females, 16/27 P2 males and 14/27 P2 females exposed to 75 ppm. Other nasal effects consisted of an increase in the incidence of very slight or slight hyperplasia of the transitional epithelium in P1 and P2 males and females exposed to 25 or 75 ppm, and an increase in the incidence of very slight or slight hyperplasia and hypertrophy of the respiratory epithelium in P1 males and females exposed to 25 or 75 ppm, and in P2 males and females exposed to 75 ppm. There were no treatment-related histopathologic effects in P1 or P2 animals exposed to 5 ppm. 

 

No treatment-related effects were seen in reproductive function or pup survival. However, pup body weights of the 75 ppm exposure group were decreased on postnatal day 14-28 in both generations. There were no effects on pup body weight in rats exposed to 25 or 5 ppm. The effects on pup body weight, as well as the changes in parental body weight and feed consumption, likely were secondary changes all stemming from nasal irritation and resultant stress. 

 

In summary, the no-observed-adverse-effect concentration (NOAEC) for parental systemic toxicity was determined to be 5 ppm (= ca. 0.018 mg/L) and was based on histologic changes in the nasal tissues seen at higher concentrations. The NOAEC for developmental toxicity was 25 ppm (= ca. 0.089 mg/L), based on decreases in pup body weight at 75 ppm which were secondary to parental toxicity. The NOAEC for reproductive toxicity was 75 ppm (= ca. 0.268 mg/L), the highest concentration tested. 

 

Butyl acrylate

For n-butyl acrylate an extended one generation study according to OECD 443 and GLP was performed. 30 Crl:CD(SD) rats were exposed to 20, 50 and 150 mg/kg bw/day by oral (gavage) exposure route (Acrylate Reach TF, 2017).

There were no test substance-related effects on survival for F0 and F1 animals at any dosage level. No test substance-related clinical observations were noted for F0 and F1 animals at any dosage level. Mean body weights, body weight gains, food consumption, and food efficiency in the 20, 50, and 150 mg/kg/day F0 and F1 males and females were unaffected by test substance administration. No test substance-related effects were noted on F0 reproductive performance (male and female mating and fertility, male copulation, and female conception indices), the mean number of days between pairing and coitus, mean gestation lengths, or the process of parturition. In addition, there were no test substance-related effects on F0 or F1 estrous cyclicity or spermatogenic parameters (testicular and epididymal sperm concentrations, sperm production rate, sperm motility, and sperm morphology) at any dosage level.

There were no test substance-related effects on the number of F1 pups born, live litter size, percentage of males at birth, F1 postnatal survival, clinical observations, anogenital distance,

offspring body weights, necropsy findings, or developmental landmarks (areolae/nipple retention, vaginal patency, and balanopreputial separation).

No test substance-related effects on clinical pathology parameters (hematology, coagulation, serum chemistry, and urinalysis) were noted for F0 and F1 animals at any dosage level. In addition, no test substance-related effects on serum levels of T4 (thyroxine) or TSH (thyroid stimulating hormone) were noted in F0 and F1 males or females or F1 pups (on PND 4 and 21). Test substance-related histologic changes were observed in all dosage groups in the F0 generation and F1 males and females in Cohort 1A. Epithelial hyperplasia and/or hyperkeratosis was observed in the nonglandular stomach in all test substance-treated groups examined. Mild to moderate changes in the 150 mg/kg/day group males and females of the F0 and F1 generations were considered adverse in this study. Microscopic changes in the stomach were associated with the gross observation of thickened nonglandular stomach, but were not associated with any clinical pathology, organ, or body weight changes. In the F0 generation, a nonadverse increased incidence of biliary hyperplasia (males and females) and random hepatocellular necrosis (males) were observed in the liver in the 150 mg/kg/day group. Additionally, nonadverse test substance-related microscopic findings (increased severity of mineralization at the corticomedullary junction) were observed in the kidneys of the 150 mg/kg/day group F0 females. Thickened stomachs were noted in the 50 and 150 mg/kg/day group F1 males and in the 150 mg/kg/day group F1 females at the scheduled necropsies for Cohort 1B; this finding was considered test substance-related and adverse in the 150 mg/kg/day group males and females. No other test substance-related internal findings were observed at any dosage level for F1 Cohort 1B animals. No test substance-related effects on the mean number of F0 implantation sites or number of unaccounted-for sites were noted at any dosage level. No test substance-related macroscopic findings were observed in F1 pups that were found dead, culled on PND 4, or examined at the scheduled necropsy on PND 21; F1 pup organ weights on PND 21 were unaffected by test substance administration. No test substance-related effects on ovarian primordial follicle counts were noted in the F0 females suspected of reduced fertility or F1 Cohort 1A females. There were no test substance-related effects on organ weights noted for F0 and F1 males and females at any dosage level.

Due to the absence of systemic toxicity noted for F0 and F1 males and females throughout the study, a dosage level of 150 mg/kg/day, the highest dosage level evaluated, was considered to be the no-observed-adverse-effect level (NOAEL) for F0 and F1 male and female systemic toxicity when n-butyl acrylate was administered orally by gavage to Crl:CD(SD) rats. Epithelial hyperplasia and/or hyperkeratosis in the nonglandular stomach noted in the 150 mg/kg/day group F0 and F1 males and females were considered adverse; based on these results, 50 mg/kg/day was considered to be the NOAEL and 150 mg/kg/day was considered to be the lowest-observed-adverse-effect level (LOAEL) for local effects in the F0 and F1 generations. Based on the lack of effects noted for F1 litters, a dosage level of 150 mg/kg/day was considered to be the NOAEL for neonatal toxicity. There was no evidence of reproductive toxicity at any dosage level based on evaluation of reproductive performance in the F0 generation and sperm measurements and estrous cyclicity in the F0 and F1 generations. Therefore, the NOAEL for F0 and F1 reproductive toxicity was considered to be 150 mg/kg/day.

 

Conclusion on fertility:Based on the data derived from the sub-chronic and chronic toxicity studies, Ethyl acrylate is not expected to impair reproduction. Furthermore,the lack of reproductive toxicity observed for Methyl and n-Butyl acrylate and the corresponding alcohol metabolites derive from the source substances indicates that theuncertainties associated with the read-across based prediction for the reproductive toxicity of EA are minimal.

Effects on developmental toxicity

Description of key information
No indications of a developmental toxic / teratogenic effect were seen in animal studies with ethyl acrylate and its structural analogues methyl or n-butyl acrylate.
Additional information

Developmental Toxicity

There are two well documented and acceptable studies available for the assessment of the developmental toxicity of ethyl acrylate in rats. Developmental toxicity studies by the oral route of administration, or in rabbits (any route) on ethyl acrylate are not available. However, a lack of developmental toxicity concern was demonstrated inthe available developmental toxicity studies in rats.

There is a data gap for developmental toxicity for EA in a second species and read-across to the structural analogues, Methyl acrylate and n-Butyl acrylate, is applied to predict its developmental toxicity properties in this species. Two guideline prenatal developmental toxicity studies in rabbits are available for these acrylate esters.

Ethyl acrylate

First, the developmental toxicity of ethyl acrylate was evaluated in Sprague-Dawley rats after inhalation exposure for 6 hours/day, on gestation days 6 to 20 (Saillenfait et al., 1999). The exposure concentrations were 0, 25, 50, 100, or 200 ppm (corresponding to 0, 0.10, 0.21, 0.41, or 0.82 mg/L). Dose groups consisted of 17 to 19 pregnant rats. No maternal deaths were observed during the study. Significant decreases in maternal body weight throughout exposure to 200 ppm were observed. There was no significant difference in the numbers of implantation sites and live fetuses, in the incidence of non-live implants and resorptions, or in the fetal sex ratio. Fetal body weights were significantly reduced at 200 ppm (7-8 % lower than control). No treatment-related increase in embryo/fetal lethality or fetal malformations was observed at any dose level. The incidence of external, visceral, and skeletal variations was similar to controls. The NOAEC for maternal and fetal toxicity was 100 ppm (0.41 mg/L) and the LOAEC was 200 ppm (0.82 mg/L). The NOAEC for developmental toxicity and teratogenicity was 200 ppm (0.82 mg/L), the highest exposure concentration tested.

Second, pregnant Sprague-Dawley rats were exposed to 0, 50, or 150 ppm of ethyl acrylate (corresponding to 0, 0.21, 0.62 mg/L) for 6 hours/day during days 6 through 15 of gestation (the period of major organogenesis). Maternal toxicity as evidenced by decreased body weight gain, decreased food consumption and increased water consumption was noted among rats exposed to 150 ppm of ethyl acrylate. No maternal toxicity was evident in pregnant females exposed to ethyl acrylate at the 50 ppm level. External and internal examination of pups did not reveal a statistically significant increase in any major malformation, but a low incidence of malformed fetuses was observed at the 150 ppm level of ethyl acrylate. Based on these data, inhalation of ethyl acrylate vapours by rats at a concentration of 50 or 150 ppm during major organogenesis was not considered to be teratogenic. In the presence of maternal toxicity at 150 ppm, a slight increase (not statistically significant) in malformed fetuses was observed. At 50 ppm, there was neither maternal toxicity nor an adverse effect on the developing embryo and fetus of rats. Thus, the NOAEC for maternal toxicity was 0.21 mg/L, and for developmental toxicity and teratogenicity 0.62 mg/L in this study, again the highest exposure concentration tested (IATG 1980).

Methyl acrylate

A prenatal developmental toxicity study in rabbits as second species was conducted with the structural analogue methyl acrylate according to OECD TG 414 for the Acrylate Task Force (BAMM 2009). 25 inseminated female Himalayan rabbits per group were whole-body exposed for 6 hrs/day, 5 days/week over a time period of 23 consecutive days (gestation days (GD) 6–28) to methyl acrylate vapours at target concentrations of 0, 5, 15, and 45 ppm. Analytical concentrations of 4.9, 15.7, 44.2 ppm (corresponding to approx. 0.0174, 0.0553, 0.1556 mg/L) were measured. On gestation day 29 the does were sacrificed and submitted to gross and histopathological examination (nasal cavities, larynx, trachea, lungs, mediastinal lymph nodes, all gross lesions). Examinations of ovaries and uterine content of the does included: determination of the weight of the unopened uterus, of the number of corpora lutea, of the number and distribution of implantation sites, and calculations of conception rate and pre- and post-implantation losses. Fetal examinations were performed on all fetuses per litter (external, soft tissue, skeletal) except head examinations that were done on half of the fetuses per litter.

 

There were no test substance-related effects on the does concerning food consumption, gross/net body weight, gestational parameters, uterine, placental and lung weights, as well as necropsy observations up to and including a dose of 45 ppm. The test substance caused a severe degeneration and atrophy of the olfactory epithelium at at least one focal area in the nasal cavity (distal levels III and/or IV) at the high-dose level (45 ppm). Though being local effects, such massive findings in the respiratory tract are likely to cause a considerable amount of distress in the affected maternal animals. Since distress is supposed to influence maternal homeostasis, this is considered to be a significant adverse effect on the maternal organism. The NOAEC for maternal toxicity was 15 ppm (0.0553 mg/L). Fetal examinations revealed no influence of the test compound on sex distribution of the fetuses and fetal body weights. Methyl Acrylate (MA) had no adverse effect on prenatal development of offspring at any of the dose levels tested (5, 15 and 45 ppm). Thus, the NOAEC for developmental effects (fetotoxicity) and the NOAEC for developmental effects (teratogenicity) was the highest concentration tested of 45 ppm (0.1556 mg/L).

Butyl acrylate

An oral developmental toxicity study in rabbits according to OECD414 and GLP was performed with n-butyl acrylate (Acrylate REACH TF, 2017). 25 inseminated New Zealand White rabbits were exposed orally (gavage) to 50, 150 and 400 mg/kg bw/day during gestation days 7 through 28. All females in the control, 50, 150, and 400 mg/kg/day groups survived to the scheduled necropsy. No test substance-related clinical observations were noted at the daily examinations or approximately 1 hour following dose administration at any dosage level.

A test substance-related absence of a mean body weight gain (0 g) was noted in the 400 mg/kg/day group on the first day of dose administration (gestation day 7-8) and resulted in a 78.9% lower mean body weight gain in this group compared to the control group during gestation days 7-10 and a lower mean body weight gain when the entire treatment period (gestation days 7-29) was evaluated.  However, the aforementioned differences were not statistically significant and were not of sufficient magnitude to affect mean body weights at this dosage level, and therefore were considered test substance-related but nonadverse. In addition, lower mean food consumption was noted in the 400 mg/kg/day group during gestation days 7-10 and resulted in lower mean food consumption in this group compared to the control group when the entire treatment period (gestation days 7-29) was evaluated; however, these differences were not statistically significant and were not of sufficient magnitude to affect mean body weights at this dosage level, and therefore were considered test substance-related but non-adverse. Mean maternal body weights, body weight gains, and food consumption in the 50 and 150 mg/kg/day groups and mean body weights, net body weights, net body weight gains, and gravid uterine weights in the 50, 150, and 400 mg/kg/day groups were unaffected by test substance administration. There were no substance-related macroscopic findings noted at the scheduled necropsy on gestation day 29 in the 50, 150, and 400 mg/kg/day groups. Intrauterine growth and survival in the 50, 150, and 400 mg/kg/day groups were unaffected by test substance administration. In addition, no test substance-related external, visceral, and skeletal malformations or developmental variations were noted at any dosage level.

Non-adverse lower mean body weight gains and corresponding lower mean food consumption were noted in the 400 mg/kg/day group. No evidence of developmental toxicity was noted at 50, 150, and 400 mg/kg/day. Based on these results, a dosage level of 400 mg/kg/day, the highest dosage level tested, was considered to be the noobservedadverseeffect level (NOAEL).

Conclusion on developmental toxicity:Overall, a lack of developmental toxicity is observed in all studies with EA, MA and nBA. The available developmental toxicity information for the common metabolite AA and the alcohol metabolites of these acrylate esters do not show any concern for developmental toxicity as discussed above.

 

Toxicity for reproduction conclusion

Due to the similarity in the toxicity profiles across the acrylate category and for the corresponding alcohols, together with the rapid metabolism rates observed in the comparative hydrolysis and GSH conjugation assays, the uncertainties associated with the read-across based prediction of reproductive toxicity of EA are considered to be minimal.Overall, the read-across is applied with a high level of confidence.

Justification for classification or non-classification

EU classification according to Annex VI of Directive 67/548/EEC: no classification required

GHS classification (GHS UN rev.3, 2009): no classification required

Additional information