Urea sulphate

Endpoint summary

Description of key information

Uronium hydrogen sulphate is not considered to be harmful by oral or dermal route:

- Oral LD50 > 2000 mg/kg bw (rat)

- Dermal LD50 > 2000 mg/kg bw (rat, no mortality observed)

No data by inhalation is available. However there is a low potential for inhalation exposure.  In addition, the substance has been demonstrated to be of low toxicity by dermal and oral routes of exposure. Dermal route is more appropriate as skin contact in production and/or use is likely. Testing for acute inhalation toxicity is therefore not justified on scientific grounds or based on exposure considerations.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Target and source substances are highly similar, both structurally and chemically.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld
- Age at study initiation: no data
- Weight at study initiation: between 153g and 171g
- Fasting period before study: yes
- Housing: transparent macrolone cages (floor area 810 cm²) with three animals in each cage.
- Diet: free access to pelleted diet "Altromin 1324"
- Water: free access to bottles with domestic quality drinking water, which was acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: at least 30% and preferably not exceed 70%
- Air changes: 10 times/hour
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: from 6 July 2010 to 1 September 2010

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle: 10 ml/kg bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION: no data

CLASS METHOD
- Rationale for the selection of the starting dose: litterature value

No. of animals per sex per dose:

300 and 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> each rat was observed 30 minutes, 2 hrs, 4 hrs and 6 hrs after the administration and thereafter daily
> the body weight was determined on days 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All six animals survived at a dose of 300 mg/kg bw. One rat per group died after the administration of the test item in a dose of 2000 mg/kg bw.

Clinical signs:

other: 300 mg/kg bw: huntched posture and piloerection on the day of application after 30 minutes; 2 hrs and 4 hrs. After 6 hrs the rats still showed piloerection. From day 1 to the end of the observation period on day 14 all animals were free of any abnormaliti

Gross pathology:

There were no pathological signs detected in the necropsy with the exception of the following findings:
- the rat no. 7 had died in the night from day 2 to day 3 and it was clearly discernible that the other animals in the cage had eaten from the body already. Feeding traces were seen on the heart, lungs, abdomen and liver. The gastrointestinal tract was filled.
- In the rat no. 12 (2000 mg/kg bw, died on day 1) bloody stomach contents, slightly edematous intestinal wall and bluish extremities were noted.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Oral LD50 > 2000 mg/kg bw

Executive summary:

In an acute oral toxicity study (OECD 423, GLP), groups of fasted Wistar rats (2x3 female/dose) were given a single oral dose of uronium hydrogen sulphate in water at doses of 300 and 2000 mg/kg bw and observed for 14 days.

 

Oral LD50 Females > 2000 mg/kg bw

All six animals survived at a dose of 300 mg/kg bw. One rat per group died after the administration of the test item in a dose of 2000 mg/kg bw.

Huntched posture and piloerection were observed on the day of application in each group.

The development of the body weight was normal in surviving animals.

There were no pathological signs detected in the necropsy in the surviving animals. In animals dead during the study, the following findings were observed:

-         the other animals in the cage had eaten from the body of the dead animal;

-         bloody stomach contents, slightly edematous intestinal wall and bluish extremities in the other rat.

 

Uronium hydrogen sulphate is of low toxicity based on the LD50 in females. The test item is not classified for acute oral toxicity according to EU criteria (DSD and CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Target and source substances are highly similar, both structurally and chemically.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH (Sulzfeld)
- Age at study initiation: no data
- Weight at study initiation: 224 - 268 g
- Fasting period before study: no
- Housing: transparent macrolone cages with two or three in each cage, males and females separated
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70%
- Air changes: 10 times / hour
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From June 22th to July 28th 2010

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flank
- % coverage: 6 x 8 cm
- Type of wrap if used: 4-layer gauze pack, fixed with Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (ca. 1.3 ml/kg bw)
- Concentration: undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> observations: each rat was observed 1, 3 and 6 hours after the start of the application and thereafter once daily
> Body weight: on days 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

Neither female nor male rats died on account of the treatment or showed severe sign of toxicosis.

Clinical signs:

other: All animals showed piloerection on day 0 after 1 hours and normal behaviour after 3 hours as well as 6 hours. From day 1 to the end of the observation period on day 14 no abnormalities were revealed.

Gross pathology:

The post mortem inspection revealed no pathological abnormalities.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Dermal LD50 > 2000 mg/kg bw in rats

Executive summary:

In an acute dermal toxicity study (OECD 402, GLP), a group of Wistar rats (5/sex) was dermally exposed to undiluted uronium hydrogen sulphate for 24 hours at the dose of 2000 mg/kg bw. Animals then were observed for 14 days.

 

Dermal LD50 (Males/Females) > 2000 mg/kg bw (no mortality observed)

 

No effects were observed on mortality, body weight gain and gross pathology.

No clinical signs were observed, except at 1 hour after application (piloerection in all animals).

 

Based on this study, uronium hydrogen sulphate is of low toxicity and is not classified as dangerous for acute dermal toxicity according to EU criteria (DSD or CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

Data are conclusive for oral and dermal route, but not sufficient for classification according to CLP criteria (Regulation (EC) No 1272/2008). No data is available by inhalation.

No classification is proposed for acute toxicity according to CLP.