Isobutyl (S)-2-chloropropionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

day of application: between 1983-10-14 and 1983-11-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study (non-GLP).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Principles of method if other than guideline:

BASF-Test, principally according to OECD guideline 401.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

83216-15-8

IUPAC Name:

83216-15-8

Details on test material:

- Name of test material (as cited in study report): L-chloropropionic acid isobutyl ester
No further data.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
male and female Wistar rats
- Source: Dr. K. Thomae, Biberach, Germany
- Age at study initiation: no data
- Weight at study initiation: group mean body weights: 196-199 g (males), 181-188 g (females)
- Fasting period before study: yes. Food was withdrawn 16 h prior to dosing but the animals still received water ad libitum
- Housing: 5 per cage, steel wire mesh cages, type DK III (Becker)
- Diet (ad libitum): Kliba laboratory diet, Klingentalmühle, Kaiseraugst, Switzerland
- Water (ad libitum): tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
0.5% aqueous carboxymethylcellulose
- Concentration in vehicle: 5.62 - 26.10% (w/v)
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

562, 1000, 1780, 2610 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology

Statistics:

LD50 was calculated by Probit analysis (Finney DJ (1971). Probit Analysis, Cambridge University Press, 3rd. ed.).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 490 mg/kg bw

95% CL:

1 150 - 1 880

Remarks on result:

other: slope factor: 1.50

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 650 mg/kg bw

95% CL:

970 - 3 990

Remarks on result:

other: slope factor: 1.85

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 1 780 mg/kg bw

Remarks on result:

other: 5% significance level

Mortality:

Totally, 1/10, 9/10, and 8/10 rats given 1000, 1780, and 2610 mg/kg bw, respectively, died. All deaths have to be considered as late deaths. For details, see table below.

Clinical signs:

other: Clinical signs of toxicity were observed in rats treated with 1780 and 2610 mg/kg bw. In males treated with 2610 and 1780 mg/kg bw, dyspnea, apathy, staggering, atony, paresis, twitching, piloerection, imbalance, and poor general state were observed. Sym

Gross pathology:

In decedents (males and females), general congestive hyperemia and occasionally contentless stomach and gut was observed. No pathological findings were noted in survivors that had been sacrificed at the end of the observation period.

Any other information on results incl. tables

Table 1: mortality rates

a) males

Dose [mg/kg]	2610	1780	1000	562
No. of rats	5	5	5	5
Dead animals after
1 h	0	0	0	0
1 d	0	0	0	0
2 d	0	0	0	0
7 d	3	4	1	0
14 d	3	4	1	0

b) females

Dose [mg/kg]	2610	1780	1000	562
No. of rats	5	5	5	5
Dead animals after
1 h	0	0	0	0
1 d	0	0	0	0
2 d	0	0	0	0
7 d	5	5	0	0
14 d	5	5	0	0

Table 2: group mean body weights [g]

a) males

dose[mg/kg]	2610	1870	100	562
start of the study	196	198	198	199
after 3 d	164	164	201	240
after 7 d	160	180	236	258
after 13 d	213	220	266	285

b) females

dose[mg/kg]	2610	1870	100	562
start of the study	181	188	187	187
after 3 d	160	151	190	217
after 7 d	-	-	211	223
after 13 d	-	-	223	235

Applicant's summary and conclusion

Executive summary:

The test substance was suspended in 0.5% aqueous CMC and administered by gavage to groups of 5 male and 5 female Wistar rats. The animals received doses of 562, 1000, 1780, and 2610 mg/kg bw and were observed for 14 days.

Mortality was 1/10, 9/10, and 8/10 in the groups given 1000, 1780, and 2610 mg/kg bw, respectively. All deaths were late deaths. Clinical signs of toxicity were noted at 1780 and 2610 mg/kg bw and comprised dyspnea, apathy, staggering, atony, paresis, twitching, piloerection, imbalance, and poor general state were observed. Symptoms were observed first at 3 days post dose and partially persisted until day 13 post dose. Animals of the two highest dose groups initially lost weight; but survivors recovered within the observation period. Pathological examination revealed general congestive hyperemia and occasionally contentless stomach and gut in decedents whereas no pathological findings were noted in survivors.