Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with isopropanolamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No studies are available on the reproduction toxicity of LAS MIPA. The endpoint was addressed with data from LAS Na and MIPA.

LAS Na:

LAS Na (C10 -14; CAS 69669 -44 -9) was fed for 84 days to 4 groups of weanling rats for two years (three generations) at doses of 14, 70, 350 mg/kg bw/day. No significant effects were observed even at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was determined to be 350 mg/kg bw/day (0.5%) (Buehler et al., 1971).

MIPA:

In a combined repeated dose oral toxicity study with a reproduction/developmental screening study (OECD 422), Wistar rats (12/sex/dose) were administered the hydrochloride salt of MIPA (CAS 7780 -04 -3) at 0, 100, 300 or 1000 mg/kg bw/day by oral gavage (BASF AG, 2008). The duration of treatment covered a 2 -week premating period and mating period in both sexes, approximately 2 weeks post-mating in males, and the entire gestation period and 4 days of lactation in females, resulting in a total of 38 and 45 exposure days for males and females, respectively. Clinical pathology examinations revealed slightly, but statistically significant reduced hemoglobin and hematocrit values, which are indicative of a mild anemic process, in high dose males. Other (minor) clinical and pathological findings appear to be incidental and not dose-related. Based on the mild anemic process in males, the NOAEL for systemic toxicity is 300 mg/kg bw/day. No adverse effects were found on reproductive and fertility parameters, thus a NOAEL of 1000 mg/kg bw/day (the highest dose tested) was established for effects on fertility in males and females.

Short description of key information:

Two studies were available addressing this endpoint for LAS MIPA: one with LAS Na (CAS 69669-44-9) and one with the hydrochloride salt of MIPA (CAS 7780-04-3). No effects on fertility/reproduction parameters were seen. No NOAEL is set.

Justification for selection of Effect on fertility via oral route:

No effects were observed on reproduction parameters. The NOAELs set in the studies were only based on systemic toxicity and hence, they are not relevant for this endpoint. No NOAEL for reproductive effects is set.

Effects on developmental toxicity

Description of key information

The toxicity data available did not show any effects on development after oral exposure to HCl MIPA. In the studies with LAS Na, marginal teratogenic effects were seen at doses of maternal toxicity. The effect was not considered to be a clear-cut developmental effect and it was associated with maternal toxicity. Therefore, no NOAEL is set for the developmental toxicity of LAS MIPA.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No studies are available on the developmental toxicity of LAS MIPA. The endpoint was addressed with data from LAS Na and MIPA.

LAS Na:

Pregnant female mice were exposed to LAS via gavage on days 6 -15 of gestation. Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Because of the very wide range between the 2 mg/kg and 300 mg/kg doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. The NOAEL for teratogenicity was 300 mg/kg bw/day (Palmer et al., 1971)

Pregnant female rats were given LAS orally in distilled water from gestation days 6 to 15 at doses of 0.2, 2, 300, 600 mg/kg bw/day. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. The NOAEL was set at 300 mg/kg bw/day both for maternal toxicity and teratogenicity (Palmer et al., 1975).

Based on the results of the aforementioned studies LAS Na is not considered to be a developmental toxicant.

MIPA:

In a combined repeated dose oral toxicity study with a reproduction/developmental screening study (OECD 422), Wistar rats (12/sex/dose) were administerd the hydrochloride salt of MIPA (CAS 7780 -04 -3) at 0, 100, 300 or 1000 mg/kg bw/day by oral gavage (BASF AG, 2008). The duration of treatment covered a 2 -week premating period and mating period in both sexes, approximately 2 weeks post-mating in males, and the entire gestation period and 4 days of lactation in females, resulting in a total of 38 and 45 exposure days for males and females, respectively. Clinical pathology examinations revealed slightly, but statistically significant reduced hemoglobin and hematocrit values, which are indicative of a mild anemic process, in high dose males. Other (minor) clinical and pathological findings appear to be incidental and not dose-related. Based on the mild anemic process in males, the NOAEL for systemic toxicity is 300 mg/kg bw/day. No adverse effects were found on reproductive and fertility parameters, thus a NOAEL of 1000 mg/kg bw/day (the highest dose tested) was established for effects on fertility in males and females.

 

Justification for selection of Effect on developmental toxicity: via oral route:

No effects on development were detected in the study with HCl MIPA. In the studies with LAS Na, marginal teratogenic effects were seen at doses of maternal toxicity. The effect was not considered to be a clear-cut developmental effect and it was associated with maternal toxicity.

Justification for classification or non-classification

Based on the available data, for LAS Na and MIPA, LAS MIPA does not need to be classified for effects on fertility and developmental toxicity according to Annex I of Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.