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Key value for chemical safety assessment

Effects on fertility

Description of key information
No information available.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP and Guideline Study
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

SIKA Hardener LI was assessed in a reproduction/developmental toxicity screening test according to OECD guideline 421. SIKA Hardener LI was administered orally (by gavage) to CRL:(WI)BR rats at repeated doses of 35, 350 and 1000 mg/kg bw/day compared to control animals, for 28 days in the male animals and up to 52 days in female animals. The dose setting was based on findings obtained in previous studies (see section 7.2 and 7.5). The test item was formulated in PEG400 at concentrations of 8.75, 87.5 and 250 mg/mL, corresponding to a 2 mL/kg bw dose volume. Analysis of dose formulations (concentration and homogeneity) were conducted during the first and last week of treatment of the study from all the concentrations employed. Recovery showed that dose formulations were homogenous and concentrations within an acceptable range of 100 ± 10 % (actual range 105-93% of nominal). Repeated administration of SIKA Hardener LI did not result in any treatment related clinical effects in parent animals. No adverse or toxicologically significant effects were noted and mean body weight, body weight gain and food consumption in treated groups compared to control animals. There were no significant differences between control and test item treated groups for reproductive ability or in mating, fertility or gestation indices and duration of the mating period. Successful coitus (sperm positive vaginal smears and/or vaginal plugs) generally occurred within up to 5 days of pairing (cohabitation). No test item effect on the duration of pregnancy was observed. The females generally littered in 22 to 23 days. All the parturitions were normal. There were no adverse effects, or biologically significant variations of the parameters related to pregnancy, parturition or post-partal period noted in the treated groups at dose levels up to and including 1000 mg/kg bw/day compared to control animals. There were no test item-related alterations in the delivery data of treated dams compared to controls. The number of corpora lutea was similar in the treated groups compared to controls. The mean number of implantation sites appeared to be lower in treated groups, but this observation had no statistical significance was within historical controls, thus, not considered toxicologically significant. Total mortality (%) mean value was apparently higher than control in the low and high dose treated groups, without attaining statistical significance and with no dose response. In the low dose group, this was likely due to a relatively high intrauterine mortality in one of the female animals. In the high dose group, the high intrauterine mortality was due to a high pre-implantation mortality in 2 females. In all the other females the preimplantation, intrauterine and total mortality values were low, within the historical control range and similar in the treated and control groups, thus, these changes were considered incidental and not regarded as an effect of the treatment. No test item-related macroscopic or microscopic findings were observed and no treatment-related organ weight changes. The no observed adverse effect level (NOAEL) for SIKA Hardener LI for parental effects was 1000 mg/kg bw/day. For reproduction parameters, no effects were noted at any dose level, resulting in a NOAEL of 1000 mg/kg bw/day.


Short description of key information:
SIKA Hardener LI was tested in a reproduction/developmental toxicity screening test according to OECD guideline 421. The no observed adverse effect level (NOAEL) for SIKA Hardener LI for parental effects was 1000 mg/kg bw/day (limit dose). For reproduction parameters, no effects were noted at any dose level, resulting in a NOAEL of 1000 mg/kg bw/day. For pup growth rate and adverse effects the NOAEL was 1000 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
only one study available

Effects on developmental toxicity

Description of key information
SIKA Hardener LI was tested in a developmental toxicity /  teratogenicity study according to OECD guideline 414. The no observed adverse effect level (NOAEL) for SIKA Hardener LI for maternal as well as for developmental effects was 1000 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP and OECD Guideline study
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

In a study conducted according to OECD Guideline 414, groups of of 24 sperm-positive female Hsd. Brl. Han: Wistar rats were treated with SIKA Hardener LI by oral administration (gavage) daily at three dose levels of 0, 200, 400 and 1000 mg/kg bw/day from day 5 up to and including day 19 post coitum. The treatment volume was 4 mL/kg bw and PEG 400 was used as vehicle. The test item did not cause death, adverse clinical signs and necropsy findings in the dose groups. SIKA Hardener LI did not reveal any adverse effect on the pregnancy, body weight, corrected body weight, and food consumption data of the dams, on the gravid uterine weight, the intrauterine mortality of the conceptuses, the number of viable fetuses and their sex distribution, the fetal and placental weight. SIKA Hardener LI did not increase the incidence of external and visceral and skeletal variations and caused no external, visceral or skeletal malformations in the fetuses. Based on these observations the No Observed Effect Level (NOEL) was determined as follows:

NOEL maternal toxicity: 400 mg/kg bw/day

NOEL developmental toxicity: 1000 mg/kg bw/day

Based on these observations the No Observed Adverse Effect Level (NOAEL) was determined as follows:

NOAEL maternal toxicity: 1000 mg/kg bw/day

NOAEL developmental toxicity: 1000 mg/kg bw/day.

SIKA Hardener LI was also assessed in a reproduction/developmental toxicity screening test according to OECD guideline 421 and draft OECD guidance document 43. SIKA Hardener LI was administered orally (by gavage) to CRL:(WI)BR rats at repeated doses of 35, 350 and 1000 mg/kg bw/day compared to control animals, for 28 days in the male animals and up to 52 days in female animals. The dose setting was based on findings obtained in previous studies (see section 7.2 and 7.5). The test item was formulated in PEG400 at concentrations of 8.75, 87.5 and 250 mg/mL, corresponding to a 2 mL/kg bw dose volume. Analysis of dose formulations (concentration and homogeneity) were conducted during the first and last week of treatment of the study from all the concentrations employed. Recovery showed that dose formulations were homogenous and concentrations within an acceptable range of 100 ± 10 % (actual range 105-93% of nominal).

The postnatal mortality (%) of pups mean values were low, showed minor differences with no dose response between the test item treated groups and were neither considered toxicologically significant, nor related to test item administration. There were no abnormalities in pups that were ascribed to the treatment: litter examination did not reveal any clinical, or macroscopic test item-related effects compared to observations noted in the control group. SIKA Hardener LI administration had no adverse effect on the mean or total number of pups, or pup survival index. The sex ratio was similar in the control and treated groups and no external gross abnormalities were observed.

In conclusion, under the conditions of this study, the no observed adverse effect level (NOAEL) for SIKA Hardener LI for developmental effects was 1000 mg/kg bw/day.


Justification for selection of Effect on developmental toxicity: via oral route:
only one study available

Justification for classification or non-classification

Based on the results of the reproduction/developmental toxicity screening test and the prenatal developmental toxicity study SIKA Hardener LI was not classified and labelled according to Directive 677548/EEC (DSD) and to Regulation (EC) No 1272/2008 (CLP).