Thymidine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Toxi-Coop ZRT.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: crystalline

Details on test material:

- Name of test material: Thymidine

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult rats, females were nulliparous and non-pregnant
- Weight at study initiation: Body weight range in preliminary study at starting: 201 - 205 g, body weight range in main study at starting 270 - 297 g (male) and 219 - 276 g (female)
- Fasting period before study: No
- Housing: During acclimatization 3 animals/sex/cage and during the study animals were housed individually. Housing in type II polypropylene/polycarbonate rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 12 days in preliminary study, 26 days in main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 8-12 air exchanges/hour by central air-condition system.
- Photoperiod (hrs dark / hrs light): Artificial light, from 6 a.m. to 6 p.m.

IN-LIFE DATES:
- From: 02 Oct. 2012
- To: 16 Oct. 2012

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Details on dermal exposure:

TEST SITE
- Area of exposure: Ca. 10 % area of the total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 24-hour exposure period any residual test item was removed using body temperature water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw (limit dose)
- For solids, paste formed: No

VEHICLE
- Vehicle used: None, test item was applied as such

Duration of exposure:

24 hour exposure

Doses:

Preliminary study: 5, 50, 300, 2000 mg/kg bw
Main study: 2000 mg/kg bw (limit dose)

No. of animals per sex per dose:

Preliminary study: 2 females
Main study: 5 males/5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day. The body weight was recorded on day 0 (shortly before the treatment) in preliminary study and on day 0 (just before the treatment), on day 7 and on day 14 with a precision of 1 g in main study.
- Necropsy of survivors performed: Yes
- Other examinations performed: Careful clinical observation was made at the following intervals: 1h, 5h after the treatment and once each day for 14 days thereafter. Individual observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern as well. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

Not applicable.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality were observed over a 14-day period following a 24-hour dermal exposure to the test item in male and female rats.

Clinical signs:

No behavioural changes, symptoms of dermal irritation and corrosion or signs of systemic toxicity were noted during the study.

Body weight:

The mean body weight of the all animals corresponded to their species and age throughout the study.

Gross pathology:

All animals survived until the scheduled necropsy on Day 14. Pale coloured kidneys as an internal necropsy finding were found in one male animal. Moderate hydrometra was found in two animals. The macroscopic finding in one male could not be related the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly. The observed hydrometra is physiological finding and connected to the cycle of the animal.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No mortalities occurred after a single 2000 mg/kg bw dermal dose. Throughout the 14-day observation period there were no systemic toxic clinical signs at both sexes and no any related effect of the test item found in body weights and body weight gains of animals. Under the experimental conditions, the acute dermal LD50 value of the test item proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats. The LD0 was determined to be 2000 mg/kg bw.

Executive summary:

An acute dermal toxicity study was performed according to EU Method B.3, OECD Guideline 402 (Acute Dermal Toxicity) and OPPTS 870.1200. A limit test was carried out. Single groups of male and female Crl:(WI)BR rats (n=5 animals/sex) were exposed to the test item at 2000 mg/kg bw (limit dose) by dermal route. The test item was applied in original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred during the study. Neither male nor female animals treated at 2000 mg/kg bw showed behavioral changes. No signs of systemic toxicity were observed during the study. No signs of irritation and corrosion were noted. The body weight development was undisturbed in all animals. No macroscopic alterations of organs related to systemic toxic effects of the test item were noted during necropsy.

Under the experimental conditions the acute dermal LD50 value of the test item proved to be > 2000 mg/kg bw in male and female Crl:(WI)BR rats. The LD0 was determined to be 2000 mg/kg bw.