Urea

Endpoint summary

Description of key information

12-month carcinogenicity screening studies in the rat and mouse demonstrate that urea is of very low chronic toxicity by the oral route. Similarly, no evidence of local or systemic toxicity was seen in 4-week and 25-week dermal toxicity studies in the rat. No clear toxicity was seen in dogs administered high doses of urea by subcutaneous injection over a period 45 days.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published NCI screening study: 12-month duration; limited investigations

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: NCI screening study

Principles of method if other than guideline:

12 month screening carcinogenesis study, with limited assessment of toxicity

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

C57BL

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals were obtained from Charles River and randomly assigned to dose groups. Animals were 6 weeks old when assigned to the study and were group housed (5/sex/cage). Food and water were available ad libitum. The mean ambient air temperature was 23°Cand a 12-hour light/dark cycle was maintained. Diets were prepared weekly.

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

12 months

Frequency of treatment:

Continuous (ad libitum)

Remarks:

Doses / Concentrations:
4500, 9000, 45000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

50/sex

Control animals:

yes, plain diet

Positive control:

Not required

Observations and examinations performed and frequency:

Animals were exposed to urea for 12 months, followed by a 4-month recovery period. Individual bodyweights were recovered pre-test and at termination. Cage weights were recorded weekly during the study.

Sacrifice and pathology:

Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues were investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

There were no signs of toxicity; bodyweights and survival were unaffected by treatment. Necropsy did not reveal any effects of treatment.

Dose descriptor:

NOAEL

Effect level:

45 000 ppm

Sex:

male/female

Basis for effect level:

other: No effects were observed at the highest dose level (4.5% in the diet)

Critical effects observed:

not specified

No evidence of toxicity was seen in this study at dose levels of up to 45000 ppm.

Conclusions:

Urea is of low toxicity following chronic administration to the mouse.

Executive summary:

In a 12 -month carcinogenicity screening assay, C57BL/6 mice (50/sex/group) were exposed to urea in the diet at concentrations of 4500, 9000 or 45000 ppm for 12 months. Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues were investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no signs of toxicity. Survival and bodyweights were unaffected by treatment. Gross and microscopic pathology did not reveal any treatment-related effects. It is concluded that urea is of very low chronic toxicity.

Reference 2

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published NCI screening study: 12-month duration; limited investigations

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: NCI screening study

Principles of method if other than guideline:

12 month screening carcinogenesis study, with limited assessment of toxicity

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals were obtained from Charles River and randomly assigned to dose groups. Animals were 6 weeks old when assigned to the study and were group housed (5/sex/cage). Food and water were available ad libitum. The mean ambient air temperature was 23°C and a 12-hour light/dark cycle was maintained. Diets were prepared weekly.

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

12 months

Frequency of treatment:

Continuous (ad libitum)

Remarks:

Doses / Concentrations:
4500, 9000, 45000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

50/sex

Control animals:

yes, plain diet

Positive control:

Not required

Observations and examinations performed and frequency:

Animals were exposed to urea for 12 months, followed by a 4-month recovery period. Individual bodyweights were recored pre-test and at termination. Cage weights were recorded weekly during the study.

Sacrifice and pathology:

Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues were investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrified after the 4-month recovery period and investigated histopathologically.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

There were no signs of toxicity; bodyweights and survival were unaffected by treatment. Necropsy did not reveal any effects of treatment.

Dose descriptor:

NOAEL

Effect level:

45 000 ppm

Sex:

male/female

Basis for effect level:

other: No effects were observed at the highest dose level (4.5% in the diet)

Critical effects observed:

not specified

No evidence of toxicity was seen in this study at dose levels of up to 45000 ppm.

Conclusions:

Urea is of low toxicity following chronic administration to the rat.

Executive summary:

In a 12 -month carcinogenicity screening assay, F344 rats (50/sex/group) were exposed to urea in the diet at concentrations of 4500, 9000 or 45000 ppm for 12 months. Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues were investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no signs of toxicity. Survival and bodyweights were unaffected by treatment. Gross and microscopic pathology did not reveal any treatment-related effects. It is therefore concluded, based on the results of this study, that urea is of very low chronic toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 250 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

reliable

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published literature study.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Subacute toxicity of urea (28-days) by dermal exposure

GLP compliance:

no

Remarks:

: older, published study

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No information available

Type of coverage:

not specified

Vehicle:

other: formulated as an ointment

Details on exposure:

Applied to back skin, an area of 20cm² in size

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No information available

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
10%, 20%, 40%
Basis:
other: level of urea in ointment

No. of animals per sex per dose:

No information available

Control animals:

not specified

Details on study design:

Urea ointment was applied at three concentrations applied to 20cm² area of back skin for 4 weeks

Observations and examinations performed and frequency:

Bodyweights were measured weekly, food and water consumption were measured at regular intervals. Clinical chemistry and haematology parameters were assessed in terminal blood samples; urinalysis parameters were also assessed.

Sacrifice and pathology:

Gross pathology and organ weights (liver, brain, heart, spleen, kidneys, pituitary, thyroid, thymus, adrenals, ovary, uterus, testes, prostate, seminal vesicles. Histopathology was also performed.

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

The authors note a number of effects in intermediate dose groups. They conclude that, compared to controls, there were no pathological changes in any organ, general symptoms, clinical chemistry, haematology or urinalysis parameters or pathological findings in treated groups.

Dose descriptor:

conc. level: 40% ointment

Sex:

male/female

Basis for effect level:

other: No dose-dependent toxicity observed

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Critical effects observed:

not specified

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Conclusions:

No effects of treatment were observed in this study.

Executive summary:

Urea (formulated as an ointment) was applied to the shorn dorsal skin of groups of male and female Wistar rats for 28 days. Bodyweights were measured; food and water consumption were assessed. Clinical chemistry, urinalysis and haematological parameters were investigated. At necropsy, organ weights were recorded; gross necropsy and histopathology were performed.

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Reference 2

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published literature study.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Subchronic toxicity of urea (25 weeks) by dermal exposure

GLP compliance:

no

Remarks:

: older, published study

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No information available

Type of coverage:

not specified

Vehicle:

other: formulated as an ointment

Details on exposure:

Applied to back skin, an area of 20cm² in size

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No information available

Duration of treatment / exposure:

25 weeks

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
10%, 20%, 40%
Basis:
other: level of urea in ointment

No. of animals per sex per dose:

No information available

Control animals:

not specified

Details on study design:

Urea ointment was applied at three concentrations applied to 20cm² area of back skin for 25 weeks

Observations and examinations performed and frequency:

Bodyweights were measured weekly, food and water consumption were measured at regular intervals. Clinical chemistry and haematology parameters were assessed in terminal blood samples; urinalysis paramters were also assessed.

Sacrifice and pathology:

Gross pathology and organ weights (liver, brain, heart, spleen, kidneys, pituitary, thyroid, thymus, adrenals, ovary, uterus, testes, prostate, seminal vesicles. Histopathology was also performed.

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

The authors note a number of effects in intermediate dose groups. They conclude that, compared to controls, there were no pathological changes in any organ, general symptoms, clinical chemistry, haematology or urinalysis parameters or pathological findings in treated groups.

Dose descriptor:

conc. level: 40% ointment

Sex:

male/female

Basis for effect level:

other: No dose-dependent toxicity observed

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Critical effects observed:

not specified

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Conclusions:

No effects of treatment were observed in this study.

Executive summary:

Urea (formulated as an ointment) was applied to the shorn dorsal skin of groups of male and female Wistar rats for 25 weeks. Bodyweights were measured; food and water consumption were assessed. Clinical chemistry, urinalysis and haematological parameters were investigated. At necropsy, organ weights were recorded; gross necrospy and histopathology were performed.

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Species:

rat

Quality of whole database:

reliable

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Reference 1

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published literature study.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Subchronic toxicity of urea (25 weeks) by dermal exposure

GLP compliance:

no

Remarks:

: older, published study

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No information available

Type of coverage:

not specified

Vehicle:

other: formulated as an ointment

Details on exposure:

Applied to back skin, an area of 20cm² in size

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No information available

Duration of treatment / exposure:

25 weeks

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
10%, 20%, 40%
Basis:
other: level of urea in ointment

No. of animals per sex per dose:

No information available

Control animals:

not specified

Details on study design:

Urea ointment was applied at three concentrations applied to 20cm² area of back skin for 25 weeks

Observations and examinations performed and frequency:

Bodyweights were measured weekly, food and water consumption were measured at regular intervals. Clinical chemistry and haematology parameters were assessed in terminal blood samples; urinalysis paramters were also assessed.

Sacrifice and pathology:

Gross pathology and organ weights (liver, brain, heart, spleen, kidneys, pituitary, thyroid, thymus, adrenals, ovary, uterus, testes, prostate, seminal vesicles. Histopathology was also performed.

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

The authors note a number of effects in intermediate dose groups. They conclude that, compared to controls, there were no pathological changes in any organ, general symptoms, clinical chemistry, haematology or urinalysis parameters or pathological findings in treated groups.

Dose descriptor:

conc. level: 40% ointment

Sex:

male/female

Basis for effect level:

other: No dose-dependent toxicity observed

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Critical effects observed:

not specified

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Conclusions:

No effects of treatment were observed in this study.

Executive summary:

Urea (formulated as an ointment) was applied to the shorn dorsal skin of groups of male and female Wistar rats for 25 weeks. Bodyweights were measured; food and water consumption were assessed. Clinical chemistry, urinalysis and haematological parameters were investigated. At necropsy, organ weights were recorded; gross necrospy and histopathology were performed.

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Reference 2

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published literature study.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Subacute toxicity of urea (28-days) by dermal exposure

GLP compliance:

no

Remarks:

: older, published study

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No information available

Type of coverage:

not specified

Vehicle:

other: formulated as an ointment

Details on exposure:

Applied to back skin, an area of 20cm² in size

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No information available

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
10%, 20%, 40%
Basis:
other: level of urea in ointment

No. of animals per sex per dose:

No information available

Control animals:

not specified

Details on study design:

Urea ointment was applied at three concentrations applied to 20cm² area of back skin for 4 weeks

Observations and examinations performed and frequency:

Bodyweights were measured weekly, food and water consumption were measured at regular intervals. Clinical chemistry and haematology parameters were assessed in terminal blood samples; urinalysis parameters were also assessed.

Sacrifice and pathology:

Gross pathology and organ weights (liver, brain, heart, spleen, kidneys, pituitary, thyroid, thymus, adrenals, ovary, uterus, testes, prostate, seminal vesicles. Histopathology was also performed.

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

The authors note a number of effects in intermediate dose groups. They conclude that, compared to controls, there were no pathological changes in any organ, general symptoms, clinical chemistry, haematology or urinalysis parameters or pathological findings in treated groups.

Dose descriptor:

conc. level: 40% ointment

Sex:

male/female

Basis for effect level:

other: No dose-dependent toxicity observed

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Critical effects observed:

not specified

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Conclusions:

No effects of treatment were observed in this study.

Executive summary:

Urea (formulated as an ointment) was applied to the shorn dorsal skin of groups of male and female Wistar rats for 28 days. Bodyweights were measured; food and water consumption were assessed. Clinical chemistry, urinalysis and haematological parameters were investigated. At necropsy, organ weights were recorded; gross necropsy and histopathology were performed.

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Species:

rat

Quality of whole database:

reliable

Additional information

Repeated dose oral toxicity

In 12 -month carcinogenicity screening assays (Fleischman et al, 1980), F-344 rats and C57BL/6 mice (50/sex/group) were exposed to urea in the diet at concentrations of 4500, 9000 or 45000 ppm for 12 months. Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues was investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no signs of toxicity. Survival and bodyweights were unaffected by treatment. Gross and microscopic pathology did not reveal any treatment-related effects. It is concluded that urea is of very low chronic toxicity. Using default conversion factors, the dose level of 45000 ppm is calculated to be equivalent to approximately 2250 mg/kg bw/d in the rat and 6750 mg/kg bw/d in the mouse.

Repeated dose dermal toxicity

In 4 -week and 25 -week dermal toxicity studies, urea (formulated as an ointment) was applied to the shorn dorsal skin of groups of male and female Wistar rats. Bodyweights were measured; food and water consumption were assessed. Clinical chemistry, urinalysis and haematological parameters were investigated. At necropsy, organ weights were recorded; gross necropsy and histopathology were performed. No dose-dependent toxicity was observed. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology (Sato et al, 1977).

Repeated exposure inhalation toxicity

Urea is demonstrated to be of very low toxicity by the oral and subcutaneous routes. The substance is a non-volatile solid produced as crystals with particle sizes of >0.1 mm. There is therefore no potential for inhalation exposure. The data requirement is therefore waived on scientific grounds and on exposure considerations. Testing is additionally not justified on animal welfare grounds.

Repeated dose toxicity by other routes of exposure

Twelve unilaterally nephrectomised dogs were injected subcutaneously with 10% urea solution (3000-4000 mg/kg bw) every 8 hours over a period of 45 days. Administration led to increased diuresis, plasma urea levels were 200 - 700 mg/100ml. The dogs displayed mild drowsiness. Haematocrit, platelet counts and EEG were not affected. The study indicates that urea is of very low toxicity in the dog following repeated administration (Balestri et al, 1971).

Justification for classification or non-classification

No classification is proposed. Urea only showed signs of very low chronic toxicity.