Methenamine

Endpoint summary

Description of key information

The LD50 ofmethenamineis > 20000 mg/kgbwafter single oral administration to rats. The LD50 ofmethenamineafter dermal application in the rats is > 2000 mg/kgbw.

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

Study period:

1966

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: old public available literature, non GLP, non Guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The study was conducted in 1966 before OECD Guidelines existed. Public available literature. No guideline indicated but similar to OECD limit test, but with two doses. For details on method see IUCLID5 materials and methods section.

GLP compliance:

no

Test type:

other: no data

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

adult rats were used.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

An 80% aqueous solution was administered by oral intubation.

Doses:

10 g/kg and 20 g/kg

No. of animals per sex per dose:

five animals per group (sex not indicated)

Control animals:

not specified

Details on study design:

Two groups of five rats were given 10 g/kg and 20 g/kg of methenamine as an 80% aqueous solution by oral intubation.

Statistics:

not indicated.

Preliminary study:

no data on preliminary study

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Sex:

not specified

Dose descriptor:

other: NOAEL

Effect level:

>= 20 000 mg/kg bw

Mortality:

no mortality observed.

Clinical signs:

other: not indicated

Gross pathology:

not indicated

Other findings:

not indicated

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of methenamine is > 20000 mg/kg bw after single oral administration to rats.

Executive summary:

In an acute oral toxicity study, 2 groups of adult Wistar rats (5 animals per dose) were given a single oral dose of methenamine (80 %) in water at doses of 10000 and 20000mg/kg bw.

Oral LD50 > 20000 mg/kg bw

All animals survived.

Hexamethylenetetramine is of practically no toxicity based on the LD50 in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

20 000 mg/kg bw

Quality of whole database:

old public available literature, non GLP, non Guideline

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according to guidelines.

Additional information

Oral:

Key study:

In an acute oral toxicity study (Della Porta, 1966), 2 groups of adult Wistar rats (5 animals per dose) were given a single oral dose of methenamine (80 %) in water at doses of 10000 and 20000 mg/kg bw. The Oral LD50 was > 20000 mg/kg bw. All animals survived. Methenamine is of practically no toxicity based on the LD50 value noted in rats.

Supporting studies:

- In an acute oral toxicity study (Dreyfors, 1989), groups of rats were given a single oral dose of methenamine. The oral toxicity of methenamine is very low based on an LD50 of 9200 mg/kg bw in rats.

- In an acute oral toxicity study (Vujosevic, 1986), groups of C3H mice were given a single oral dose methenamine. Oral LD50 = 1853 mg/kg bw

The lower values reported by Vujosevic (1986) are not considered relevant, as the studies have too many limitations. This view is supported by the EU RAR. Methenamine is of low Toxicity based on the LD50 in mice.

Dermal:

Key study:

In an acute dermal toxicity study (Berthold, 1997), groups of young adult HsdCpb: WU rats (5/sex) were dermally exposed to methenamine (99.3 %) in water for 24 hours to the shaved shoulder region at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50

Males > 2000 mg/kg bw

Females > 2000 mg/kg bw

Combined > 2000 mg/kg bw

No mortality occurred. The only clinical finding was a yellowish discoloured application site in all male and female rats. The finding started on day 1 after application and was still present at the end of the 14-day observation period. At necroscopy no alterations were detected.

Methenamine is not toxic, when applied to the skin of rats.

Inhalation:

No studies available.

In accordance with column 2 of REACH Annex VIII, the test acute toxicity after inhalation (required in section 8.5) does not need to be conducted as acute toxicity studies for oral and dermal application are available. Inhalation exposure is regarded negligible as no particles below 125 µm were detected in particle size analysis (see section 4.5).

Human Data:

Systemic toxicity was not observed.

Conclusion:

Limited data on the acute toxicity of methenamine in humans are available.

Acute toxicity in rats was demonstrated to be very low after oral and dermal application with LD50 values of > 20 g/kg bw and 2 g/kg bw, respectively. Data on inhalation toxicity of methenamine are not available, and not needed as exposure via inhalation (as gas or aerosol) is not likely to occur.

Justification for selection of acute toxicity – oral endpoint
Study with highest reliability

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of REACH Annex VIII, the test acute toxicity after inhalation (required in section 8.5) does not need to be conducted as acute toxicity studies for oral and dermal application are available. Inhalation exposure is regarded negligible as no particles below 125 µm were detected in particle size analysis (see IUCLID5 section 4.5).

Justification for selection of acute toxicity – dermal endpoint
Only key study available.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified under Regulation (EC) No 1272/2008.