Reaction mass of (R)-cyano(3-phenoxyphenyl)methyl rel-(1R,3R)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate and (R)-cyano(3-phenoxyphenyl)methyl rel-(1S,3S)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate

Acute Toxicity: oral

Administrative data

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: Study similar to guideline with minor restrictions and under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Five male and five female rats per dose group were used.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (R)-cyano(3-phenoxyphenyl)methyl rel-(1R,3R)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate and (R)-cyano(3-phenoxyphenyl)methyl rel-(1S,3S)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate

EC Number:

932-389-6

Molecular formula:

C23H19ClF3NO3

IUPAC Name:

Reaction mass of (R)-cyano(3-phenoxyphenyl)methyl rel-(1R,3R)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate and (R)-cyano(3-phenoxyphenyl)methyl rel-(1S,3S)-3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate

Test animals

Species:

rat

Strain:

other: Alderley Park SPF-derived albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Unit, ICI PLC, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: 5-7 weeks
- Weight at study initiation: males: 133-175 g, females: 112-152 g
- Fasting period before study: 17-20 h
- Housing: at a maximum of 5 in stainless steel cages
- Diet (e.g. ad libitum): Porton Combined Diet, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 21°C
- Humidity (%): 55%
- Air changes (per hr): 20-30
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The dose level was altered by varying the concentration of the dosed preparation.

Doses:

nominal: 25, 100, 200, 300, and 400 mg/kg bw
analytical: 25.3, 98, 196, 294, and 335 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females were used per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: at about 1 and 5 h after dosing and then daily until day 15
- Frequency of weighing: at day 0 (before dosing), the day of dosing (day 1), and on day 3, 4, 8, and 15

Statistics:

The acute oral LD50 values and the 95% confidence limits were calculated by the probit method.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

166 mg/kg bw

Based on:

test mat.

95% CL:

52 - 318

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

114 mg/kg bw

Based on:

test mat.

95% CL:

33 - 191

Mortality:

No animal died in the 25.3 mg/kg bw dose group but all animals died or were killed in extremis in the 335 mg/kg bw dose group. At the remaining dose levels the proportion of the animals not surviving varied . All deaths occurred between days 1 and 4. Mortality data are given in table 1.

Clinical signs:

other: Clinical signs of toxicity were observed in most of the animals at all dose levels within 6 h of dosing and persisted up to day 8 (most animals), 11 (one animal) or 13 (two animals). Most common effects were decreased activity, dehydration, piloerection,

Any other information on results incl. tables

Table 1: Cumulative mortality data for rats after single administration of cyhalothrin; five males and 5 females were used per dose group.

Day	Dose [mg/kg bw] and cumulative mortality
	25.3	98	196	294	335
Males
1	0	0	0	0	1
2	0	2	0	2	3
3	0	2	2	3	5
15	0	2	2	3	5
Females
1	0	0	0	0	1
2	0	3^b)	1	3	4^a)
3	0	3	3	3	5
4	0	3	3	4^a)	5
15	0	3	3	4	5

^a)       one animal was killed in extremis

^b)       two animals were killed in extremis

 

Table 2: Mean bodyweight data for surviving rats after single administration of cyhalothrin.

	Day of weighing, mean bodyweight [g] and number of animals						Bodyweight gain day 0-15 [g]
	0	1	3	4	8	15
Males
25.3 mg/kg	147 5	131 5	157 5	164 5	198 5	256 5	109
98 mg/kg	152 3	139 3	145 3	155 3	18 3	256 3	104
196 mg/kg	153 3	138 3	140 3	148 3	188 3	246 3	93
294 mg/kg	173 2	150 2	137 2	152 2	193 2	266 2	93
Females
25.3 mg/kg	140 5	124 5	147 5	150 5	169 5	200 5	60
98 mg/kg	121 2	106 2	121 2	124 2	152 2	177 2	56
196 mg/kg	132 2	117 2	120 2	135 2	157 2	188 2	56
294 mg/kg	141 1	123 1	119 1	131 1	159 1	206 1	65

 

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The study is considered to be reliable with restrictions.

Executive summary:

The acute oral toxicity of cyhalothrin was determined in a study similar to OECD 401 and under GLP. Five males and five females were used per dose group.

 The LD50 (rat, oral) was determined to be 166 mg/kg bw in males and 114 mg/kg bw in females.

Clinical signs of toxicity were seen in nearly all surviving animals and included decreased activity, dehydration, piloerection, salivation, ungroomed appearance, urinary incontinence, upward curvature of the spine and ataxia.

Based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, the test item has to be classified as acute toxic category III.