6-deoxy-L-mannose

Endpoint summary

Description of key information

Oral: OECD 425; rat LC50 >5000 mg/kg. Reliability = 1

Inhalation: No study available

Dermal: OECD 402; rat LD50 >5000 mg/kg. Reliability = 1

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: U.S. FDA, Redbook 2000: IV.C.2: Acute Oral Toxicity Tests (1993)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Laboratories International, Inc., Raleigh, North Carolina, U.S.A.
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: 209.0-217.5 g
- Fasting period before study: approximately 17.5-18.25 hours prior to dosing, with food being returned to the rats approximately 2.75-3 hours after dosing
- Housing: Individually in solid-bottom caging with bedding and appropriate species-specific enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26ºC (68-79ºF)
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): approximate 12-hour light/dark cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL per kg of body weight. Individual dose volumes were calculated using the fasted body weights obtained prior to dosing.

DOSAGE PREPARATION (if unusual): The dosing formulations were sonicated prior to dose administration and stirred throughout the dosing procedure.

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily animal health observations were conducted throughout the study for mortality and signs of illness, injury, or abnormal behavior. Except as noted below, animals were weighed on test days -1, 1, 8, and 15, and were observed for clinical signs at the beginning of fasting, just before dosing (test day 1), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter. Clinical observations were inadvertently not recorded on test day 5. The daily animal health observations recorded on those days, and the clinical observations collected on the preceding and succeeding days, were sufficient to assess the animals’ conditions.
- Necropsy of survivors performed: yes

Statistics:

Not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: highest dose tested

Mortality:

No deaths occurred during the study.

Clinical signs:

other: There were no clinical abnormalities observed.

Gross pathology:

No gross lesions were present in the rats at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats): >5000 mg/kg

Executive summary:

A single dose of the test substance was administered by oral gavage to fasted female rats at a dose of 5000 mg/kg. The five rats were dosed on the same day. All rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. The rats were necropsied to detect grossly observable evidence of organ or tissue damage. There were no incidents of mortality, clinical abnormalities, or overall (test day 1-15) body weight loss. No gross lesions were present in the rats at necropsy. Under the conditions of this study, the test substance was not considered acutely toxic via the oral route of exposure in female rats at a dose level of 5000 mg/kg. In the absence of test substance related mortality, an LD₅₀ was not calculated.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

GLP, guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: MAFF Japan Test Guidelines for Agricultural Chemicals 12-Nousan-8147 (2000)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories International, Inc., Raleigh, North Carolina, U.S.A.
- Age at study initiation: approximately 9 weeks old
- Weight at study initiation: 299.0-327.9 g (males); 213.2-226-8 g (females)
- Fasting period before study: No
- Housing: Individually in solid-bottom caging with bedding and appropriate species-specific enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C) :20-26ºC (68-79ºF)
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): approximate 12-hour light/dark cycle

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 37 square centimeters
- % coverage: approximately 10 percent of the total body surface area of rats in the 200 - 300 g body weight range
- Type of wrap if used: 2-ply gauze patch. The rats were then wrapped with stretch gauze bandage and self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with paper towels soaked in warm water
- Time after start of exposure: Approximately 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg of body weight
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

5000 mg/kg

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: The rats were weighed on test days 1, 8, and 15, and were observed daily for clinical signs of toxicity and dermal irritation (weekends and holidays excluded for dermal irritation). The rats were reshaved as needed during the study.
- Necropsy of survivors performed: yes

Statistics:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: highest dose tested

Mortality:

There were no incidents of mortality.

Clinical signs:

other: One male exhibited scabbing on the back (inside of the test site) between test days 6-15 and discolored skin on the back between test days 6-7. Between test days 12-15, a wound on the right shoulder was observed in one male. Epidermal scaling (inside the

Gross pathology:

Gross findings were present in 2/5 male animals, which correspond to the clinical observations noted above. One male had a skin ulcer/erosion present on the back at the outer edge of the treated skin area. The other male had a single skin ulcer/erosion present on the right shoulder. No other gross findings were observed.

Other findings:

There were no instances of edema or erythema observed.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rats): >5000 mg/kg

Executive summary:

A single dose of the test substance was applied to the shaved, intact skin of 5 male and 5 female rats at a dose level of 5000 mg/kg of body weight. The application site was covered with a semi-occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage at the end of the 15-day test period.

There were no incidents of mortality and no overall (test day 1-15) body weight losses among any animals. One male exhibited scabbing on the back (inside of the test site) between test days 6-15 and discoloured skin on the back between test days 6-7. Between test days 12-15, a wound on the right shoulder was observed in one male. Epidermal scaling (inside the test site) was noted in one female between test days 6-8. No other clinical abnormalities were observed. There were no instances of oedema or erythema observed. Gross findings were present in 2/5 male animals, which correspond to the clinical observations noted above. One male had a skin ulcer/erosion present on the back at the outer edge of the treated skin area. The other male had a single skin ulcer/erosion present on the right shoulder. No other gross findings were observed. Under the conditions of this study, the dermal LD₅₀ for the test substance was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

GLP, guieline study

Additional information

A single dose of the test substance was administered by oral gavage to fasted female rats at a dose of 5000 mg/kg in accordance with OECD Guideline 425. There were no incidents of mortality, clinical abnormalities, or overall (test day 1-15) body weight loss. No gross lesions were present in the rats at necropsy. Under the conditions of this study, the oral LD50 for the test substance was greater than 5000 mg/kg.

 

A single dose of the test substance was applied to the shaved, intact skin of 5 male and 5 female rats at a dose level of 5000 mg/kg of body weight in accordance with OECD Guideline 402. There were no incidents of mortality and no overall (test day 1-15) body weight losses among any animals. One male exhibited scabbing on the back (inside of the test site) between test days 6-15 and discoloured skin on the back between test days 6-7. Between test days 12-15, a wound on the right shoulder was observed in one male. Epidermal scaling (inside the test site) was noted in one female between test days 6-8. No other clinical abnormalities were observed. There were no instances of oedema or erythema observed. Gross findings were present in 2/5 male animals, which correspond to the clinical observations noted above. One male had a skin ulcer/erosion present on the back at the outer edge of the treated skin area. The other male had a single skin ulcer/erosion present on the right shoulder. No other gross findings were observed. Under the conditions of this study, the dermal LD50 for the test substance was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.

Justification for classification or non-classification

Based on the oral and dermal LD50 in rats of >5000 mg/kg, no classification is required for acute oral or dermal endpoints according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.