Clorofene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 Jun - 12 Jul 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted in 1981

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted in 1987

Deviations:

no

GLP compliance:

no

Test type:

other: acute oral toxicity

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Clorofene

EC Number:

204-385-8

EC Name:

Clorofene

Cas Number:

120-32-1

Molecular formula:

C13H11ClO

IUPAC Name:

clorofene

Test animals

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (U.K.) Limited
- Age at study initiation: about 40 days
- Weight at study initiation: 118 - 206 g (males), 120 - 164 g (females)
- Housing: 5 animals of the same sex per cage in high density polypropylene cages (56 x 38 x 18 cm) with stainless steel grid floors and top
- Diet: Laboratory Diet No. 1, pelleted (K and K Greeff Chemicals Ltd.), ad libitum (except for the removal of food approximately 18 h before rats were given the test material by gavage)
- Water: tap water, ad libitum
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (18 - 25 acceptable limits)
- Humidity (%): 55 (40 - 65 acceptable limits)
- Air changes (per hr): approximately 17
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

1500, 2500, 3150, 3969 and 5000 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: Animals were observed at least at three separate inspections during the first hour after administration and twice daily after Day 2. Inspection for decedents was conducted three times daily and two times at weekends. Individual bodyweights were determined on the day before dosing and on Days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Acute median lethal dose, 95% confidence interval and slope of the dose response curve for both sexes was determined by probit analysis. When probit analysis failed to demonstrate a linear dosage/mortality response curve, the LD50 and 95% confidence interval were calculated using the method of moving average interpolation after Thompson.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

4 462 mg/kg bw

Based on:

test mat.

95% CL:

>= 4 383 - <= 4 545

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 852 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 128 - <= 4 838

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 147 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 783 - <= 4 608

Mortality:

1500 and 2000 mg/kg bw: no mortalities occured
3150 mg/kg bw: 1/5 female died (at 1 - 3 day post dose)
3969 mg/kg bw: 1/5 male died (at 1 - 5 day post dose) and 2/5 females died (at 1 - 3 day and 1 - 4 day post dose)
5000 mg/kg bw: 4/5 males died (at 2 - 2 day and 2 - 3 day post dose) and 5/5 females died (at 1 - 2 day, 2 - 3 day, 1 - 4 day post dose)

Clinical signs:

1500 mg/kg bw: ungroomed appearance (Day 2)
2500 mg/kg bw: ungroomed appearance (Day 2)
3150 mg/kg bw: diarrhoe, hunched posture and decreased motor activity (between 30 min and 1 h post dose); ungroomed appearance (Day 2)
3969 mg/kg bw: diarrhoe, hunched posture and decreased motor activity (between 30 min and 1 h post dose); ungroomed appearance (Day 2)
5000 mg/kg bw: diarrhoe, hunched posture and decreased motor activity (between 30 min and 1 h post dose); transient periods of irritability and hyperpnoea (during 30 min post dose in occasional decedents); ungroomed appearance and pigmented staining of the snout (Day 2)

All surviving animals at 2500 mg/kg bw or more continued to show ungroomed appearance for varying length of time up to Day 7. Several animals amongst the higher treatment groups also displayed pigmented staining of the snout until Day 4. Other infrequently observed signs during this period included pigmented orbital secretion and thin body conformation. No abnormality was observed after Day 7.

Body weight:

No effect on body weight was noted.

Gross pathology:

Necropsy of decedents revealed abnormal gastrointestinal contents in the majority of animals. Superficial staining of the mouth, nares, forelimbs, head, urogenital area or general body surfaces was also observed in many animals. Other less frequently noticed gross pathological findings included congestion or haemorrhage of the thymus, slight congestion or incomplete collapse of the lungs and congestion of the brain.
Necropsy of survivors revealed fibrous adhesions between the stomach and adjacent tissues of the left lobe of the liver and abdominal wall in 4 males and one female treated with 3969 mg/kg bw. A low incidence of gastrointestinal contents, slight or moderate hydronephrosis and slight congestion of the lungs was observed in rats of the lower dose groups.

Any other information on results incl. tables

Table 1: Results of acute oral toxicity testing

Males
Dose [mg/kg bw]	Toxicological results*	Duration of signs	Time of death	Mortality (%)
1500	0/5/5	Day 2	-	0
2500	0/5/5	4 h - Day 3	-	0
3150	0/5/5	1 h - Day 7	-	0
3969	1/5/5	1 h - Day 8	Day 5	20
5000	4/5/5	15 min - Day 5	Day 2	80
LD50= 4462 mg/kg bw
Females
1500	0/5/5	Day 2	-	0
2500	0/5/5	4 h - Day 3	-	0
3150	1/5/5	1 h - Day 8	Day 4	20
3969	2/5/5	1 h - Day 8	Day 3	40
5000	5/5/5	15 min - death	Day 1-2	100
LD50= 3852 mg/kg bw

* number of dead animals/number of animals with signs of toxicity/total number of animals tested

Applicant's summary and conclusion

Interpretation of results:

other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: not classified