Reaction mass of N-butylphosphorothioic triamide and N-propylphosphorothioic triamide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

One of the components of the reaction mass, namely Phosphorothioic triamide, N-butyl- (NBPT, CAS # 94317-64-3) which is present in the reaction mass at a concentration of ca. 57.9 %, is reported on the ECHA website as causing effects on fertility that were classified by the registrant as Cat. 2, H361f /R62. This classification is adapted for the reaction mass without further testing due to the NBPT-content.

Short description of key information:
One of the components of the reaction mass, namely Phosphorothioic triamide, N-butyl- (CAS # 94317-64-3) which is present in the reaction mass at a concentration of ca. 57.9 %, is reported on the ECHA website as causing effects on fertility that were classified by the registrant as Cat. 2, H361f /R62. This classification is adapted for the reaction mass without further testing due to the NBPT-content.

Effects on developmental toxicity

Description of key information

NOTOX 2011, OECD 414:
NOAEL maternal toxicity: 100 mg/kg bw/day
NOAEL developmental toxicity: 100 mg/kg bw/day
NOAEL teratogenicity: 300 mg/kg bw/day             

Effect on developmental toxicity: via oral route

Endpoint conclusion:

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

A prenatal developmental toxicity study of LIMUS-Sambaydestillation in rats by oral gavage was conducted according to OECD 414 guideline and GLP (NOTOX, 2011).

Mated female Wistar (Han) rats were assigned to four dose groups each containing 22 animals. The test item was administered once daily by gavage from Days 6 to 19 post-coitum at doses of 30, 100 and 300 mg/kg body weight/day (Groups 2, 3 and 4, respectively). Rats of the control group received the vehicle, 1% (w/w) carboxymethyl cellulose suspension in water, alone. Females were checked daily for the presence of clinical signs. Food consumption was determined at periodic intervals; body weight was

determined daily during treatment and at periodic intervals in the other periods. Formulations (Groups 1 - 4) prepared on one day during treatment were analyzed on accuracy, homogeneity and stability.

All animals surviving to Day 20 post-coitum were subjected to an examination post-mortem and external, thoracic and abdominal macroscopic findings were recorded. A laparohysterectomy was performed on each surviving female of Groups 1-4. Gravid uterine weights were recorded for all pregnant females, and net body weights and net body weight changes were calculated. The uteri,

placentae and ovaries were examined, and the numbers of live and dead fetuses, early and late resorptions, total implantations and corpora lutea were recorded. All fetuses and placentas were weighed. The fetuses were sexed and examined for external, visceral and skeletal malformations and developmental variations. All live fetuses were euthanized. One half of the fetuses was examined for

visceral anomalies and the remaining half of the fetuses was subjected to a skeletal examination.

RESULTS

Chemical analysis of dose preparations

Accuracy, homogeneity and stability of formulations were demonstrated by analyses.

Maternal findings

Treatment with LIMUS-Sambaydestillation at 300 mg/kg body weight/day resulted in one unscheduled death (killed in extremis), treatment-related clinical signs (lethargy, piloerection, hunched posture, uncoordinated movements, abnormal gait, pale feces, pale and/or lean appearance), reduced body weight/body weight gain and food consumption. At necropsy, no gross findings were noted that were considered related to treatment.

No maternal toxicity was observed at the lower dose levels of 30 and 100 mg/kg body weight/day.

Developmental findings

There were no treatment-related effects on viability, litter size and sex ratio up to 300 mg/kg body weight/day.

Reduced fetal body weights were noted for both male (statistical significant) and female (not statistically significant) fetuses at 300 mg/kg body weight/day compared to controls. This adverse effect on fetal body weight was considered related to the considerable maternal toxicity observed in the high dose group. In line with this, both mean male and female placenta weights were slightly lower

at 300 mg/kg body weight/day compared to controls (not statistically significant).

Morphological examination of the fetuses revealed neither effects on fetal external or visceral morphology nor skeletal malformations that could be related to treatment up to 300 mg/kg body weight/day.

Several skeletal variations which were indicative for a developmental delay were noted at higher incidences in the 300 mg/kg body weight/day group. These included reduced ossification of the skull, unossified sternebra nos. 5 and/or 6, unossified hyoid, bipartite ossification of vertebral centra and entire sternum unossified. In addition, the incidence of ossified cervical centrum no. 1 was decreased at 300 mg/kg body weight/day compared to the concurrent control value. The reductions in ossification

noted were not statistically significant, but while considering the decreased fetal body weights at 300 mg/kg body weight/day, it is assumed that the delayed ossification occurred in this context.

CONCLUSION

Based on the results in this prenatal developmental toxicity study both the maternal and developmental No Observed Adverse Effect Level (NOAEL) for LIMUS-Sambaydestillation were established as being 100 mg/kg body weight/day. The NOAEL for teratogenicity was 300 mg/kg body weight/day. There were no adverse fetal findings evident at a dose not producing maternal toxicity.

Justification for classification or non-classification

Based on the available data, there is no need to classify the substance for developmental toxicity/teratogenicity according to Directive 67/548/EEC and CLP. Due to the NBPT-content in the reaction mass of ca. 57.9 %, a classification with Cat. 2, H361f (CLP) and R62 (67/548/EEC) is adapted. This classification is taken from the ECHA-website from the NBPT-dossier and adapted for the reaction mass without further testing.