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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Reproductive Toxicity

NOAEL was considered to be 151 mg/kg/day for P and F1 generation when female rats were treated with test chemical orally in water.

Link to relevant study records
Reference
Endpoint:
fertility, other
Remarks:
Cardiac teratogenesis
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer reviewed journal.
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Reproductive toxicity effect of test chemical was evaluated by conducting experiment on rat.
GLP compliance:
no
Limit test:
no
Justification for study design:
No data
Species:
rat
Strain:
not specified
Sex:
female
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: drinking water
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Remarks:
drinking
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Test chemical was dissolve in drinking Water.

VEHICLE
- Justification for use and choice of vehicle (if other than water): drinking water
- Concentration in vehicle: 0 and 151 mg/kg bw
- Amount of vehicle (if gavage): 42 ml/day
- Lot/batch no. (if required): No data
- Purity: No data
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
approx 21 days (During pregnancy)
Frequency of treatment:
Daily
Details on study schedule:
not specified
Remarks:
0 and 151 mg/kg bw/day
No. of animals per sex per dose:
not specified
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data
- Cage side observations checked in table [No.?] were included: Rats were observed for mortality.

DETAILED CLINICAL OBSERVATIONS: Rats were observed for sign of toxicity.

- Time schedule: No data

BODY WEIGHT: Rats were observed for body weight.
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OTHER:
Oestrous cyclicity (parental animals):
Pregnancy complications, implantation sites, were observed
Sperm parameters (parental animals):
not specified
Litter observations:
Numbers of live or dead fetuses, fetal weight and crown-rump length were observed
Postmortem examinations (parental animals):
uterine and ovarian morphologic were examinations.
Postmortem examinations (offspring):
placental weight, no gross external or noncardiac internal organ congenital abnormalitieswere examined.
Statistics:
Using Fisher exact analysis, mean number of implantation site and resorption site for treated group and control group was estimated.
Reproductive indices:
not specified
Offspring viability indices:
not specified
Clinical signs:
no effects observed
Description (incidence and severity):
No evidence of toxicity was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No change in body weight gain was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No effect on implantation sites and resorption sites were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on live and dead fetuses were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Dose descriptor:
NOAEL
Effect level:
151 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
gross pathology
reproductive function (oestrous cycle)
reproductive performance
Remarks on result:
other: No effects were noted
Critical effects observed:
not specified
System:
other: Not specified
Organ:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: Not specified
Organ:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No efect on numbers of live or dead fetuses were observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on fetal weight were observed.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No effect on placental weight were observed.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No effect on external morphology were observed.
Histopathological findings:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No effect on crown-rump length and noncardiac internal organ congenital abnormalities were observed.
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
151 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
body weight and weight gain
organ weights and organ / body weight ratios
gross pathology
other: cardiac defects
Critical effects observed:
no
System:
cardiovascular
Organ:
heart
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
other: not specified
Reproductive effects observed:
not specified
Treatment related:
not specified

Table: Congenital cardiac Malformations

 

 

Group

Heart abnormalities

Trichloroacetaldehyde p.

(151 mg/kg bw/day)

Abnormal looping

-

Aortic hypoplasia

-

Pulmonary artery hypoplasia

-

Atrial septal defects

2

Mitral valve defects,

Hypoplasia or ectasia

2

Tricuspid valve defects,

Hypoplasia or ectasia

-

Ventricular septal defects,

Perimembranousa

Mascular

 

3

-

Atrioventricular

Septal defects

-

Pulmonary valve defects

1

Aortic valve defects

-

Situs inversus

-

Total

Abnormal Hearts

Fetuses with abnormal hearts

Fetuses

 

8

8

248


aSubaortic

Conclusions:
NOAEL was considered to be 151 mg/kg/day for P and F1 generation when female rats were treated with test chemical orally in water.
Executive summary:

The reproductive toxicity of test chemical was evaluated by conducting experiment in female rats. Test chemical was administered orally in drinking water. Chemical was given to rats during organogenesis at the concentration of 0 and 151 mg/kg bw/day. No reproductive effects were observed on health, weight gain, and pregnancy, uterine and ovarian morphologic examinations. Similarly, no effect on implantation sites, resorption sites were observed as compared to control. In addition, no developmental effect such as live and dead fetuses, fetal weight, placental weight, crown-rump length, gross external or no cardiac internal organ congenital abnormalities were observed in fetus of treated female rats. Therefore, NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
151 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is Klimicsh 2 and from peer reviewed journal.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive Toxicity

Data available from different studies were reviewed to determine the reproductive toxicity of test chemical. The studies are as mentioned below:

 

The reproductive toxicity of test chemical was evaluated by conducting experiment in female rats. Test chemical was administered orally in drinking water. Chemical was given to rats during organogenesis at the concentration of 0 and 151 mg/kg bw/day. No reproductive effects were observed on health, weight gain, and pregnancy, uterine and ovarian morphologic examinations. Similarly, no effect on implantation sites, resorption sites were observed as compared to control. In addition, no developmental effect such as live and dead fetuses, fetal weight, placental weight, crown-rump length, gross external or no cardiac internal organ congenital abnormalities were observed in fetus of treated female rats. Therefore, NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

 

In supporting with the above result, another screening test for reproductive / developmental toxicity was conducted in male and female CD-1 mice exposed to the test chemical in drinking-water at 21.3 or 204.8 mg/kg body weight per day. Animals were exposed for 3 weeks prior to breeding. Exposure of females (5 per group) continued during gestation and until pups were weaned at 21 days of age. No gross malformations were noted, and no significant effects were observed in duration of gestation, number of pups delivered, pup weight, or number of stillborn pups. All pups (15 per group) showed the same rate of development and level of performance on several neurobehavioral tests, except that pups exposed to 204.8 mg/kg body weight per day when tested at 23 days of age showed impaired retention of passive avoidance learning on both the 1-h and 24-h retention tests (P < 0.05). This study identified a NOAEL for neurodevelopmental toxicity of 21.3 mg/kg body weight per day and a LOAEL of 204.8 mg/kg body weight per day based on the impairment in passive avoidance learning. This study also identifies a NOAEL for reproductive and other developmental effects. The NOAEL for reproductive and other developmental effects of test chemical on CD-1 mice were observed to 204.8 mg/kg body weight per day.

 

Based on the data available from different studies, NOAEL was considered to be 151 mg/kg/day for reproductive toxicity, when rodents were treated with test chemical orally. Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive toxicant.

 

Effects on developmental toxicity

Description of key information

Developmental Toxicity

NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Peer reviewed journal research article
Qualifier:
according to guideline
Guideline:
other: Refer below Principle
Principles of method if other than guideline:
The developmental toxicity of test chemical was evaluated by conducting study in female rats.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: drinking water
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Details on exposure:
not specified
Analytical verification of doses or concentrations:
no
Details on mating procedure:
not specified
Duration of treatment / exposure:
Approx. 21 days (During Pregnancy)
Frequency of treatment:
Daily
Duration of test:
not specified
Remarks:
0 and 151 mg/kg bw/day
No. of animals per sex per dose:
not specified
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Maternal examinations:
Survival, Clinical sign, Weight gain, pregnancy complications and uterine complication were examined.
Ovaries and uterine content:
implantation sites and resorption site were examined.
Fetal examinations:
Live and dead fetuses. Fetal weight, placental weight, crown-rump length, and external morphology were studied.
Congenital cardiac malformations: Like Abnormal looping, Aortic hypoplasia, Pulmonary artery hypoplasia, Atrial septal defects, Mitral valve defects, Tricuspid valve defects ,Pulmonary valve defects, Atrioventricular septal defects,etc were examined.

Statistics:
Fisher exact analysis were used.
Indices:
not specified
Historical control data:
not specified
Clinical signs:
no effects observed
Description (incidence and severity):
No evidence of toxicity was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No change in body weight gain was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross pathological changes were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No effect on implantation sites were observed
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
No effect on resorption sites were observed
Early or late resorptions:
no effects observed
Description (incidence and severity):
No effect on resorption sites were observed
Dead fetuses:
no effects observed
Description (incidence and severity):
No effect on live and dead fetuses were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
There was no complications in pregnancy were observed, steady weight gain was observed. All uterine and ovarian morphologic examinations were normal.
Dose descriptor:
NOAEL
Effect level:
151 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Congenital cardiac malformations
Abnormalities:
not specified
Localisation:
not specified
Fetal body weight changes:
no effects observed
Description (incidence and severity):
No effect on fetal weight were observed.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No efect on numbers of live or dead fetuses were observed.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No effect on external morphology were observed.
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No effect on placental weight were observed.
No effect on crown-rump length and noncardiac internal organ congenital abnormalities were observed.
Dose descriptor:
NOAEL
Effect level:
151 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reduction in number of live offspring
fetal/pup body weight changes
external malformations
other: Placental weight, Crown-rump length.
Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified
Developmental effects observed:
not specified
Treatment related:
not specified

Table: Congenital cardiac Malformations

 

 

Group

Heart abnormalities

Trichloroacetaldehyde p.

(151 mg/kg bw/day)

Abnormal looping

-

Aortic hypoplasia

-

Pulmonary artery hypoplasia

-

Atrial septal defects

2

Mitral valve defects,

Hypoplasia or ectasia

2

Tricuspid valve defects,

Hypoplasia or ectasia

-

Ventricular septal defects,

Perimembranousa

Mascular

 

3

-

Atrioventricular

Septal defects

-

Pulmonary valve defects

1

Aortic valve defects

-

Situs inversus

-

Total

Abnormal Hearts

Fetuses with abnormal hearts

Fetuses

 

8

8

248


aSubaortic

Conclusions:
NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

Executive summary:

The developmental toxicity of test chemical was evaluated by conducting experiment in female rats. Test chemical was administered orally in drinking water. Chemical was given to rats during organogenesis. Test chemical dose 0 and 151 mg/kg bw/day. No reproductive effects were observed on health, weight gain, and pregnancy, uterine and ovarian morphologic examinations. Similarly, no effect on implantation sites, resorption sites were observed as compared to control. In addition, no deveplmental effect such as live and dead fetuses, fetal weight, placental weight, crown-rump length, gross external or noncardiac internal organ congenital abnormalities were observed in fetus of treated female rats. Therefore, NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
151 mg/kg bw/day
Study duration:
subacute
Species:
mouse
Quality of whole database:
Data is Klimicsh 2 and from peer reviewed journal.
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

Developmental Toxicity

The developmental toxicity of test chemical was evaluated by conducting experiment in female rats. Test chemical was administered orally in drinking water. Chemical was given to rats during organogenesis. Test chemical dose 0 and 151 mg/kg bw/day. No reproductive effects were observed on health, weight gain, and pregnancy, uterine and ovarian morphologic examinations. Similarly, no effect on implantation sites, resorption sites were observed as compared to control. In addition, no deveplmental effect such as live and dead fetuses, fetal weight, placental weight, crown-rump length, gross external or noncardiac internal organ congenital abnormalities were observed in fetus of treated female rats. Therefore, NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

Justification for classification or non-classification

Comparing the NOAEL value and effects observed on rodents, with the criteria of CLP regulation the given test chemical is not likely to classify as reproductive and developmental toxicant.

Additional information