Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

According to ECHA factsheet of 15/09/2009 ECHA considers registration dossiers for substances ≥ 1000 t/y as technically complete even if they do not contain the results of a screening study for reproductive/-developmental toxicity if the following condition is met: The dossier contains either the results of, or a testing proposal for, a prenatal developmental toxicity study and either the results of, or a testing proposal for, a 2-generation reproductive toxicity study. Testing proposals for a prenatal developmental toxicity study and for a 2-generation reproductive toxicity study were created in IUCLID sections 7.8.2 and 7.8.3. Details on the proposal can be found in the attached document. The study proposals on reproductive toxicity are still under evaluation by ECHA.

None of the main components of the reaction mass was found to be toxic for reproduction based on literature data, except for TBA, which produced skeletal anomalies in a 19 -day reproduction toxicity study (see table below). Hence, it is possible that a certain degree of developmental toxicity may also be found for the reaction mass.

Table: Reproduction toxicity data for the main components of the reaction mass from literature

 

Oral

Inhalation

Conclusion

DSBE (1)

From analogue, SBA: Rat, 8-week, 2-generation study:

NOAEL (maternal and developmental toxicity): 1771 mg/kg/day

From analogue, SBA: Rat, 20-day, prenatal developmental toxicity study: NOAEL: 3500 ppm (maternal toxicity)

NOAEL: >7000 ppm (developmental toxicity)

Overall the weight of evidence indicates that analogue sBA does not produce teratogenic (developmental) toxic effects in the developing embryo/fetus of laboratory animals. In a 2-generation study on rats, no effects of SBA on fertility were noted.

DIPE (2)

 

Rat, 20-day, prenatal developmental toxicity study: NOAEL: 430 ppm (maternal and developmental toxicity)

 

Rat, 13-week, subchronic toxicity study: NOAEL: 480 ppm (reproductive effects)

DIPE is not a teratogen. No changes in reproductive organ weights and structure or sperm and spermatid number were noted in a subchronic toxicity study.

SBA (3)

Rat, 8-week, 2-generation study: NOAEL (maternal and developmental toxicity): 1771 mg/kg/day

Rat, 20-day, prenatal developmental toxicity study:

NOAEL: 3500 ppm (maternal toxicity)

NOAEL: >7000 ppm (developmental toxicity)

SBA is not a developmental toxicant. There was no evidence of teratogenic events nor was there evidence of selective developmental toxicity. In a 2-generation study on rats, no effects on fertility were noted.

TBA (4)

Rat, 4-weeks, 1-generation study:

NOAEL (maternal toxicity) = 1000 mg/kg-bw/day

NOAEL (reproductive/developmental toxicity) = 400 mg/kg-bw/day 

 

Mouse, 22-days, prenatal developmental toxicity study:

NOAEL (maternal toxicity) = 1500 mg/kg-bw/day

LOAEL (developmental toxicity) =1125 mg/kg-bw/day

 

Mouse, 18-days, prenatal developmental toxicity study:

LOAEL (developmental toxicity) = 1550 mg/kg-bw/day

Rat, 19-day, prenatal developmental toxicity study:

NOAEL (maternal toxicity) = 15.2 mg/L

LOAEL (developmental toxicity) = 6.06 mg/L

 

A prenatal developmental toxicity study revealed significant increases in the incidence of skeletal anomalies (primarily delayed skeletal ossification) in treated offspring.

In a one-generation study, no effects on reproductive organs, mating success, fertility, or sperm quality were observed; however a slight increase in the length of gestation (significance not specified) was observed at the two highest doses. Furthermore, an increase in estrous cycle length was observed in female mice in a 13-week repeated-dose study.

 

 

(1) HIGH PRODUCTION VOLUME (HPV) CHEMICAL CHALLENGE PROGRAM TEST PLAN For sec-Butyl Ether CAS NO. 6863-58-7, Prepared by: ExxonMobil Chemical Company, November 28,2006

 

(2) ExxonMobil Chemical Company Shell Chemical LP For: American Chemistry Council, lsopropanol Panel, Diisopropyl Ether HPV Task Group December 12,2005

 

(3) OECD SIDS Dossier for Butan-2 -ol, CAS No.78 -92 -2, ExxonMobil Biomedical Sciences Inc.,09.01.2002

 

(4) Robust Summaries for t-Butanol, CAS Number 75 -65 -O USEPA HPV Challenge Program Submission April 10, 2002

Effects on developmental toxicity

Additional information

See discussion on effects on fertility.

Justification for classification or non-classification

Based on the available data on the consitutents, the reaction mass is not classified as toxic to reproduction. This will be verified with the proposed tests.