3-chloropropionyl chloride

Endpoint summary

Description of key information

In an acute oral toxicty study (similar to OECD 401) a LD50 between 1000 and 1470 mg/kg bw was derived. In an acute inhalation toxicity study a LC50 <0.90 mg/L/1h air was derived.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, similar to guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Rats (5/sex/dose) were exposed to a single oral dose (six different dose levels) of the test substance. The rats were then observed for 14 days. Mortality, body weight, and clinical signs were recorded. In addition necropsy was performed on all animals.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hagemann + Wiga
- Weight at study initiation: means of the dose groups: males: 170-250 g; females: 180-190 g
- Diet: Herilan MRH-Haltung; H.Eggersmann KG
- Fasting period before study: 15-20 hours

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2, 9.28, 13.62, 20, 29.4, and 43 % w/v
- Amount of vehicle (if gavage): 5 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

Doses:

100, 464, 681, 1000, 1470, 2150 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing was performed on day 0, day 2-4, day 7 and day 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 1 470 mg/kg bw

Based on:

test mat.

Mortality:

- No deaths occurred in animals dosed with 100, 464, 681 and 1000 mg/kg bw
- 1470 mg/kg bw: 5/5 male and 3/5 female animals died
- 2150 mg/kg bw: all animals died

Clinical signs:

other: - Animals dosed with 100 and 464 mg/kg bw were free of clinical signs - At 681 mg/kg bw reddened skin and roughed fur was observed - At 1000 mg/kg bw dyspnoea, apathy, staggering, reddened skin, roughed fur and poor general condition was observed - At 147

Gross pathology:

animals that died:
- heart: acute dilation right, acute congestive hyperaemia
- lung: acute exhalation median grade
- stomach: extensive haemorrhagic gastritis due to corrosion
- intestine: partially necrotic and partially reddened mucous membrane, content bloody

sacrificed animals:
- 100 - 681 mg/kg bw: without findings
- 1000 and 1470 mg/kg bw: forefront of the gastroesophageal vestibule thickened, isolated cases of gastroesophageal vestibule adhered to liver, spleen and peritoneum

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

Two acute oral toxicity studies were identified. The most recent study performed similar to OECD guideline 401 was chosen to assess this endpoint. The conclusions are supported by the second study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non guideline study, available as unpublished report, restrictions in design and/or reporting but otherwise adequate for assessment.

Principles of method if other than guideline:

Six rats per dose were exposed to a test substance concentration of ca. 173 ppm and 185 ppm for 1 hour by inhalation. In addition 6 rats were exposed to ca. 265 ppm for 30 minutes. The rats were then observed for 7 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

The vapors were generated by bubbling 10 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder and then diluted with 480 L/h air.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

h

Remarks on duration:

30 min and 1 h

Concentrations:

173 ppm / 0.90 mg/L (1 hour), 185 ppm / 0.96 mg/L (1 hour), and 265 ppm / 1.38 mg/L (30 min)

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology

Statistics:

no data

Sex:

female

Dose descriptor:

LC50

Effect level:

< 0.9 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

- 173 ppm: 5 out of 6 rats died
- 185 ppm: 4 out of 6 rats died
- 265 ppm: 3 out of 6 rats died

Clinical signs:

other: Attempts to escape, after 3 minutes dyspnea, irritation of the mucous membrane, gasping, surviving animals showed accelerated breath for several days.

Body weight:

no data

Gross pathology:

- Animals that died: pulmonary edema
- Sacrificed animals: sporadic chronic bronchitis

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

Three acute inhalation toxicity studies were identified. Only one derived a LC50 and was therefore chosen as most adequate to asses this endpoint.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

In an acute oral toxicity study similarly performed to OECD guideline 401, five SD rats per sex per dose were orally exposed to 100, 464, 681, 1000, 1470, 2150 mg/kg bw of the test substance by gavage followed by a 14 day observation period (1980; RL2). Mortality, clinical sings and bodyweights were recorded. In addition necropsy was performed on all animals. No deaths occurred in animals dosed with 100, 464, 681 and 1000 mg/kg bw. At 1470 and 2150 mg/kg bw 8/10 and 10/10 animals died, respectively. Animals dosed with 100 and 464 mg/kg bw were free of clinical signs. Clinical signs included reddened skin, dyspnea, apathy, abnormal position of the body, staggering, tremors, convulsion, reddened skin, scrubby fur, shortage of breath and bad general condition in the other dose groups. Animals that died showed acute heart dilation, acute congestive hyperaemia, extensive haemorrhagic gastritis due to corrosion and partially necrotic and partially reddened intestinal mucous membranes. Sacrificed animals showed thickened forefront of the gastroesophageal vestibule and isolated cases of gastroesophageal vestibule adhered to liver, spleen and peritoneum. Based on the mortality data a LD50 >1000 and <1470 mg/kg bw was derived.

In an additional acute oral toxicity study (1968; RL2), rats (10/sex/dose) were exposed orally to the test substance at concentrations of 266, 1064, 1662.5, and 2128 mg/kg bw by gavage. The rats were then observed for 7 days and the LD50 was calculated. No deaths occurred in the 266 mg/kg bw dose group. 6/20, 17/20, and 20/20 animals died in the 1064, 1662.5, and 2128 mg/kg bw dose groups, respectively. Clinical signs included face-down position, cyanosis, labored breathing, staggering gait, apathy, ruffled fur, crouched position, and convulsions. Animals that died showed effects on the snouts, liver, stomach, and kidney. Based on the mortality data an LD50 of ca 1130 mg/kg bw was derived.

Acute inhalation toxicity

In an acute inhalation toxicity study (1986; RL2) 6 rats per dose were exposed to the test substance at a concentration of ca. 173 ppm and 185 ppm for 1 hour by whole body inhalation. In addition 6 rats were exposed to ca. 265 ppm for 30 minutes. The rats were then observed for 7 days. The vapors were generated by bubbling 10 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder and then diluted with 480 L/h air. Mortality and clinical sings were recorded. In addition necropsy was performed on all animals. At 173 ppm (0.90 mg/L) 5/6 animals died and at 183 ppm (0.96 mg/L) 4/6 animals died. Of the animals exposed for 30 minutes at 265 ppm (1.38 mg/L) 3/6 animals died. Clinical signs included attempts to escape, dyspnea, irritation of the mucous membrane, gasping, surviving animals showed accelerated breath for several days. Animals that died showed pulmonary edema and sacrificed animals sporadic chronic bronchitis. The 1 hour-LC50 based on the obtained results in this study was determined to be smaller than 0.90 mg/L.

In a study similar to the previous study (1968; RL2) rats, 3 per sex, were exposed to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 1, 3 and 10 min. The acquired concentration of the test substance was 54.5 mg/L. At this concentration all animals died after an exposure of 3 or 10 minutes and two animals died exposed for 1 minute. Excitement, attempts to escape, irritation of mucous membranes, and weight loss were observed in animals exposed for 1 minute. In the 3 and 10 min exposure groups, corneal opacity, gasping, irritation of mucous membranes, and dyspnea was observed. Gross pathology revealed pulmonary edema, emphysema and some lungs were blood filled.

In another acute inhalation toxicity study, the 50% respiration rate decrease (RD50) was determined (1997; RL4). 4 CD-1 mice per dose group were exposed to the test substance via inhalation at concentrations of 49, 70, 136, or 160 mg/m3 for 30 minutes. The observation period lasted 7 days and clinical signs, body weight, respiration rate and macroscopic examination was performed. During exposure a decrease in respiration rate was observed. In all groups, a slight reduction in body weight was observed on the day after exposure. Macroscopic examination revealed in mouse of the top three concentration groups gray discolored lungs. The RD50 was determined to be 72 - 73 mg/m3.

Justification for classification or non-classification

Based on an oral LD50 of > 1000 and < 1470 mg/kg bw the test substance has to be classified for Acute toxicity Cat 4: H302: Harmful if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Based on an inhalation 1 hour-LC50 <0.90 mg/L air the test substance has to be classified as Acute toxicity Cat 1: H330: Fatal if inhaled in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.