Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
The testing laboratory was the competent Authority. The test method is well documented and similar to OECD guideline. Although some deviations occur, the results can be considered reliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
1/3 of animals were left natural delivery and newborn evaluated for survival until day 8. No data on maternal food consumption, weight of fetus and sketelal alteration are reported.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,2-trichloro-1,2-difluoroethane
EC Number:
940-543-9
Cas Number:
354-15-4
Molecular formula:
C2HCl3F2
IUPAC Name:
1,1,2-trichloro-1,2-difluoroethane
Test material form:
other: vapour
Details on test material:
- Name of test material (as cited in study report): R122a

Test animals

Species:
rat
Strain:
not specified

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
For conception purposes, in the evening, females in the stage of proestrus and oestrus were taken to males in the ratio of 2:1.
The first day of pregnancy was determined by the presence of sperm in the vaginal smear.
Duration of treatment / exposure:
21 days
Frequency of treatment:
24h/24h
Duration of test:
Animals were treated since day 1 of pregnancy.
2/3 females from the group were slaughtered by decapitation on day 21 of pregnancy.
1/3 of animals were left till natural delivery in order to study the usefulness of the offspring. Survival of newborn rats was evaluated until day 8 from the offspring.
No. of animals per sex per dose:
20-22
Control animals:
yes, concurrent no treatment

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
decrease in the orientation response and motor activity

Maternal developmental toxicity

Pre- and post-implantation loss:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Details on maternal toxic effects:
Females showed some CNS effects (exploratory activity test) at the highest dose

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEC
Effect level:
10 mg/m³ air
Based on:
test mat.
Basis for effect level:
behaviour (functional findings)

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in litter size and weights:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects: no effects (no internal anomalies)

Effect levels (fetuses)

Key result
Dose descriptor:
NOEC
Effect level:
> 100 mg/m³ air (nominal)
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Results of the examination of rats on the 17th day of pregnancy with continuous inhalation exposure to HCFC 122a

Exposure of the body of laboratory animals to HCFC 122a at concentrations of 100 mg/m3on the 17th day of pregnancy caused a statistically significant increase in the summation-threshold value (STV) and a decrease in the orientation response and motor activity (Details are provided in the following table).

Concentrations of 10 and 1 mg/m3did not lead to changes in the parameters studied.

No.

Indicators

Concentration, mg/m3

100

10

1

Control

1.

Summation-threshold value, B

6.9 ± 0.164*

6.0 ± 0.246

5.4 ± 0.082

5.6 ± 0.16

2.

Orientation response
(number of peeking in)

5.2 ± 0.246

8.2 ± 0.328

7.8 ± 0.328

8.4 ± 0.24

3.

Exploratory activity
(number of crossings)

2.7 ± 0.246*

4.8 ± 0.328

5.0 ± 0.41

5.6 ± 0.41

4.

Motor activity
(number of risings)

5.8 ± 0.49

5.2 ± 0.328

4.6 ± 0.574

4.9 ± 0.32

5.

Rectal temperature, °С

38.2 ± 1.48

38.1 ± 0.13

37.9 ± 0.098

38.3 ± 0.1

6.

Leukocyte concentration,
х 109in L

12.4 ± 0.23

12.2 ± 0.156

11.6 ± 0.23

11.9 ± 0.2

7.

Erythrocyte concentration,
х 1012in L

7.9 ± 0.26

7.6 ± 0.164

6.8 ± 0.59

7.2 ± 0.62

8.

Hemoglobin contents, g %

13.2 ± 0.31

12.7 ± 0.377

13.6 ± 0.43

12.8 ± 0.4

* Note Р < 0.05

Results of the study of embryonic material and newborn rats obtained from female rats exposed to inhalation of HCFC 122a

The study of embryonic material, as well as indicators of condition of newborn rats of the female rats from experimental groups showed no significant difference compared with control animals (Details are provided in the following tables).

 

Results of the study of embryonic material

Indicators

Concentration, mg/m3

100

10

1

Control

Quantity:

 

 

 

 

– foetuses per one female rat

11.62 ± 0.68

11.2 ± 0.29

12.1 ± 1.2

12.8 ± 0.72

– corpora lutea of pregnancy

12.82 ± 0.52

12.08 ± 0.72

13.28 ± 0.44

13.9 ± 0.84

– implantation site

11.74 ± 0.95

11.3 ± 0.55

12.28 ± 0.24

13.02 ± 0.72

Death:

 

 

 

 

– before implantation, %

8.32 ± 0.46

6.25 ± 0.52

7.33 ± 0.48

6.46 ± 0.36

– after implantation, %

1.02 ± 0.08

0.82 ± 0.6072

1.44 ± 0.09

1.49 ± 0.12

– total, %

9.17 ± 0.84

7.08 ± 0.87

8.68 ± 0.54

8.04 ± 0.72

Foetuses:

 

 

 

 

– weight, g

3.52 ± 0.18

3.24 ± 0.24

3.32 ± 0.32

3.42 ± X not readable in the translation

– length, cm

3.84 ± 0.26

3.60 ± 0.19

3.69 ± 0.32

3.78 ±  X not readable in the translation

Placenta:

 

 

 

 

– weight, g

0.52 ± 0.02

0.50 ± 0.03

0.51 ± 0.04

0.50 ± X not readable in the translation

– diameter, cm

1.48 ± 0.03

1.46 ± 0.02

1.47 ± 0.02

1.45 ± X not readable in the translation

 

Exposure to HCFC 122a did not lead to the development of pathological effects of internal organs of foetuses compared to control animals (details in the following tables).

Thus, HCFC 122a in tested concentrations did not show embryotropic effect. The maximum concentration of 100 mg/m3was inactive.

 

Indicators of condition of newborn rats

Indicator

HCFC 122а concentrations, mg/m3

100

10

1

Control

Number of offspring

12.0 ± 0.72

11.8 ± 0.56

12.3 ± 0.84

12.6 ± 0.64

Mass, g

 

 

 

 

– initial

5.22 ± 0.28

 X not readable in the translation

± 0.18

5.48 ± 0.34

5.58 ± 0.22

– Day 8

10.98 ± 0.28

11.2 ± 0.44

11.3 ± 0.26

11.6 ± 0.44

Survival rate, %

97.2 ± 0.76

100

100

98.9 ± 0.80

 

 

Microscopic study of cross section of foetuses by Wilson method

Concentration, mg/m3

Haemothorax, %

Hemoperitoneum, %

Hemorrhage in liver, %

Edema of adipose tissue, %

100

1.20 ± 0.06

0.94 ± 0.06

0.42 ± 0.08

1.40 ± 0.08

10

0.82 ± 0.04

0.91 ± 0.06

0

0.68 ± 0.04

1

0.98 ± 0.06

0.72 ± 0.04

0.34 ± 0.06

0.80 ± 0.04

Control

1.01 ± 0.08

0.82 ± 0.04

0

1.12 ± 0.06

 

Applicant's summary and conclusion

Conclusions:
HCFC 122a in tested concentrations did not show toxic effect on fetus and offspring. The maximum tested concentration of 100 mg/m3 was inactive.
Executive summary:

The objective of the reported study was the assessment of both the reprotoxicity potential and the genotoxicity potential of HCFC 122a.

Embryotoxiceffect of HCFC 122a was studied on non-pedigree white rats exposed to round-the-clock inhalation of the substance throughout pregnancy (21 days) at concentrations of 102.8 ± 5.6 (d= 25.66), 10.4 ± 1.09 (d= 4.99), 1.2 ± 0.13 (d= 0.59) mg/m3. The lowest concentration tested corresponded to the recommended level of daily average maximum allowable concentration of HCFC 122a in the ambient air set up by the Ministry of Health of the Russian Federation; the medium concentration was 10 times higher, and the maximum concentration was at the level of maximum allowable concentrations of HCFC 122a in the working area set up by the Ministry of Health of the Russian Federation.

Each group of animals consisted of 20-22 mature females weighing 190-220 g. Control rats were in similar conditions: in chambers with clean air.

On the 17th day of pregnancy, the rats were tested on a number of integrated indicators and on day 21, 2/3 females from the group were sacrificed. 1/3 of animals were left till natural delivery in order to study the usefulness of the offspring.

 

Evaluation of embryotoxic effect was carried out: during the autopsy, the uterine horn and placenta were examined, took into account the number of corpora lutea of pregnancy in the ovary, the number of live and dead foetuses, number of resorptions, fetal and placental weight, calculated pre-implantation, post-implantation and total embryonic mortality. In order to determine the pathology of internal organs of foetuses, the Wilson method was used, modified by A.P. Dyban and co-workers.

While assessing the usefulness of offspring, the weight and number of newborn rats, their development in the post-natal period was taken into account.

 

The results of the study of embryotoxic effect showed that exposure of the body of laboratory animals to HCFC 122a at concentrations of 100 mg/m3on the 17th day of pregnancy caused a statistically significant increase in the summation-threshold value (STV) and a decrease in the orientation response and motor activity.

Concentrations of 10 and 1 mg/m3did not lead to changes in the parameters studied.

The study of embryonic material, as well as indicators of condition of newborn rats of the female rats from experimental groups showed no significant difference compared with control animals.

Exposure to HCFC 122a did not lead to the development of pathology of internal organs of foetuses compared to control animals.

Thus, HCFC 122a in tested concentrations did not have embryotoxic effect. The maximum concentration of 100 mg/m3was inactive.