Ethane, 1,1,2-trichloro-1,2-difluoro-

Developmental toxicity / teratogenicity

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

Test material information

Constituent 1

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.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/m³ air

Doses / concentrations 2

Dose / conc.:

1 mg/m³ air

Doses / concentrations 3

Dose / conc.:

10 mg/m³ air

Doses / concentrations 4

Dose / conc.:

100 mg/m³ air

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

Reduction in number of live offspring:

no effects observed

Changes in litter size and weights:

no effects observed

Details on 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:

no

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/m^3
		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 10^9in L	12.4 ± 0.23	12.2 ± 0.156	11.6 ± 0.23	11.9 ± 0.2
7.	Erythrocyte concentration, х 10^12in 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/m^3
	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/m^3
	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/m^3	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.