2-Pyridinecarboxylic acid, 4-amino-3,6-dichloro-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 June 2001 to 30 August 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Acute Dermal Toxicity Study, 2000

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-3,6-dichloropyridine-2-carboxylic acid

EC Number:

604-721-7

Cas Number:

150114-71-9

Molecular formula:

C6H4Cl2N2O2

IUPAC Name:

4-amino-3,6-dichloropyridine-2-carboxylic acid

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: tan powder

Specific details on test material used for the study:

Purity: 94.5%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: ca. 8 weeks
- Weight at study initiation: 122 - 176 g
- Housing: animals were housed two or three per cage in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 40 - 70 % (relative)
- Air changes: 12 - 15 air changes per hour
- Photoperiod: 12 hours of darkness / 12 hours of light (06:00 to 18:00)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: the test material was moistened with 0.5 % aqueous methylcellulose

Details on dermal exposure:

The dorsal side of the trunk of each rat was clipped free of fur the day prior to application of the test material. The test material, moistened with 0.3 mL of 0.5 % aqueous methylcellulose, was administered to the back of the rats (approximately 10 % of the surface area of the rats) and covered with a 6 x 6 cm gauze/cotton patch. The gauze patch was held in place by elastic tape and wrap. The wrappings were removed after approximately a 24-hour exposure period and observations were recorded for irritation at the application site. The skin was wiped thoroughly with a water-moistened soft disposable towel and dried with a soft disposable towel.

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A Detailed Clinical Observation (DCO) was conducted for all rats prior to test material administration for comparison with the observations recorded throughout the study. Animals were observed a minimum of two times on the day of treatment. A DCO was done each day (including weekends and holidays) during the study. Hand-held and open-field observations included a careful physical examination. The rats were weighed pre-study, the day of treatment and on days 2, 8, and 15.
- Necropsy of survivors performed: Yes, necropsy was performed on all animals. Animals were anaesthetised by inhalation of carbon dioxide and euthanised by decapitation after clamping of the trachea.
- Other examinations performed: The eyes were examined in situ using a moistened glass microscope slide applied to the corneal surface. Following inspection of the externum and body orifices, the nasal, cranial, oral, thoracic, and abdominal cavities were opened and the visceral organs were examined both in situ and following dissection, and tissues were not saved.

Statistics:

Means and standard deviations were calculated for body weights. The data were evaluated for statistical outliers by a sequential test (Grubbs, 1969); however, outliers were not routinely excluded from statistical analysis.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the two-week observation period.

Clinical signs:

other: Clinical observations consisted of perioral soiling in one male and two females on test day 1 or 2 and periocular soiling in one male on test day 1. There was also an abrasion or scratches observed on the dermal test site of one male and one female rat fr

Gross pathology:

There were no gross pathologic observations.

Any other information on results incl. tables

Table 1: Mean body weights (g)

	Days on test
Sex	-1	1	2	8	15
Male	168.9	173.2	162.8	200.8	227.3
Female	127.1	128.6	118.0	137.6	146.6

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal LD50 of the test material in male and female Fischer 344 rats was greater than 5000 mg/kg.

Executive summary:

The acute dermal toxicity of the test material was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF (2000).

During the study, five male and five female Fischer 344 rats received a single 24-hour exposure of 5000 mg/kg body weight of test material moistened with 0.5 % aqueous methylcellulose. Parameters evaluated during the two-week observation period included body weights, detailed clinical observations, and gross pathological changes.

All animals survived the two-week observation period. Clinical observations consisted of perioral soiling in one male and two females on test day 1 or 2 and periocular soiling in one male on test day 1. There was also an abrasion or scratches observed on the dermal test site of one male and one female rat from test day’s 2-5 or test day 4, respectively. The test material dried and adhered to these two animals, thus causing the abrasion/scratches during test material removal. All animals lost weight by test day 2, but gained weight over the remainder of the study. There were no gross pathologic observations.

Therefore, under the conditions of this study, the acute dermal LD50 of test material in male and female Fischer 344 rats was greater than 5000 mg/kg bw.