Reaction mass of 1,3-dichloropropene and 2-chloropropane and 2-chloropropene and 3-chloropropene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to O.E.C.D. Testing Guideline 403 (Acute Inhalation Toxicity) without GLP compliance.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

The exposure duration was 6 hr, not 4 hr and a full post-treatment observation period of 14 days was not followed.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropene

EC Number:

203-457-6

EC Name:

3-chloropropene

Cas Number:

107-05-1

Molecular formula:

C3H5Cl

IUPAC Name:

3-chloroprop-1-ene

Details on test material:

As per the IUCLID5 Sections 1.1. - 1.4. for 3-chloropropene.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were acquired from Charles River Breeding Laboratories, Wilmington, Massachusetts, U.S.A. and their age at study initiation was 9-14 wks. The body weight range at study initiation was males: 192 - 284 gm and females: 130 - 166 gm. Upon arrival in the laboratory, rats were housed 5/cage, immediately prior to each exposure, animals were placed in stainless steel exposure cages in groups of either 5 or 10/cage, after exposure, they were placed in their original holding cages in an animal room which was used to house the control groups, until the time of necropsy. The animals were allowed Feed (Purina Rat Chow) and water ad libitum. Their acclimation period was > 7 days. No other conditions were reported.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

The exposure apparatus were glass and stainless steel chambers with a volume 160-liters. A calculated amount of allyl chloride liquid was metered into a heated (approximately 80°C) vaporization flask with a precision syringe pump and sweeping the vapor with filtered air into the main chamber airflow at a rate of approximately 30 liters/minute.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

online monitoring: IR, timed measurements: GC-FID

Duration of exposure:

ca. 6 h

Remarks on duration:

The O.E.C.D. Testing Guideline recommends 4 hr.

Concentrations:

200, 300, 500, 800, 1000 and 2000 ppm

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Following the exposure period, the frequency of observations and weighing were as follows: pre exposure (day 0), 24 h post exposure (day 1), 48 h post exposure (day 2, 2000 ppm, males only), 72 h post exposure (day 3, 500 and 800 ppm only, both sexes). Full necropsy were performed on survivors. Organ weights for liver and kidneys were taken at necsospy. Clinical chemistry parameters measured were: BUN, SGPT, AP, SGOT and glucose. Histopathology evaluation was performed on samples of liver and kidney.

Statistics:

Body weight, clinical chemistry and organ weight data were analyzed statistically using Dunnett's test. The level of significance for all cases was p<0.05.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 1 000 - < 2 000 ppm

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: All females died at 2000 ppm.

Mortality:

All females died at the high dose level of 2000 ppm and one male animal died. One female died at 1000 ppm.

Clinical signs:

other: Diarrhia and lethargy were observed beginning at a dose level of 500 ppm and became increasing severe as the dose levels increased. Palpebral Closure and conjunctival hyperemia were sever in survivors at the top two dose levels.

Body weight:

The body weight of animals exposed to 2000 ppm was substantially reduced.

Gross pathology:

The nasal turbinate exhibited nasal discharge at 1000 ppm and at 2000 ppm they were hyperemic and/or edematous. The liver exhibited accentuated lobular pattern with or without associated pale appearance at 1000 and 2000 ppm. The kidneys exhibited pale discoloration of cortex at 300 ppm and 500 ppm, pale cortex with darker medullary junction and generally enlarged or swollen kidneys at 800 ppm and higher. The thymus showed a decreased in size at 1000 ppm and higher. The gastrointestinal tract had decreased contents and depletion of abdominal adipose tissue at 1000 ppm and higher. The testes were edematous at 1000 and 2000 ppm.

Any other information on results incl. tables

For clinical biochemical parameters only the BUN concentration shows a clear dose dependent increase becoming statistically significant at 1000 ppm in males and at 500 ppm in females at 24 h post exposure. The kidneys mean relative weights increased in all tested dose groups from 500 - 2000 ppm, and the absolute weights were raised in the 800 ppm and both 1000 ppm groups. Histopathological examination found kidney acute tubular degeneration at 300 ppm and above in females and at 500 ppm and above in males suggesting the kidney as a potential target organs.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: other: EU DSD

Conclusions:

Exposure of rats to vapors of 3-chloropeopene for 6 hr resulted in an estimated LC50 of 1000 ppm (3083 mg/m3) to < 2000 ppm (6166 mg/m3) suggesting that inhalation of 3-chloropropene may be Harmful. The kidney was identified as a potential target organ. A similar conclusion could be made for AC Light Ends.

Executive summary:

The structural analog, 3 -chloropropene was assessed for acute inhalation toxicity in the rat by a study protocol similar to O.E.C.D. Testing Guideline 403 "Acute Inhalation Toxicity". Exposure of rats to vapors of 3-chloropeopene for 6 hr resulted in an estimated LC50 of 1000 ppm (3083 mg/m3) to < 2000 ppm (6166 mg/m3) suggesting that inhalation of 3-chloropropene may be Harmful. The kidney was identified as a potential target organ. A similar conclusion could be made for AC Light Ends.