L-Histidine Hydrochloride Monohydrate

Endpoint summary

Description of key information

In an acute oral toxicity study in rats conducted according to OECD 423, the target substance L-Histidine Hydrochloride Monohydrate (HHM) showed no mortality at the limit dose of 2000 mg/kg bw. Hence, the LD50 value was considered to exceed 2000 mg/kg bw.

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:

2017-10-20 to 2018-01-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Number of animals per group: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals
- Age at start of treatment: Approx. 8 weeks
- Body weight at start of treatment: 148 to 169 g
- Identification: ear mark and tail mark with indelible ink
- Acclimatisation: at least 5 days
- Housing: up to 5 animals of the same sex and same dosing group together (in polycarbonate cages (Makrolon MIV type; height 18 cm) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J. Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany))
- Diet: ad libitum, pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: ad libitum, tap water

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 47 to 56%
- Photoperiod (hrs dark / hrs light): 12/12
- Air changes per hour: at least 10

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

A single dose of test item was administered to the appropriate animals by oral gavage on Day 1, using a syringe with a plastic gavage cannula attached (dosing volume: 10 mL/kg bw). Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
- Frequenvy of weighing: Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes, all animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded
- Clinical signs: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored.

Statistics:

No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Preliminary study:

n.a.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture, uncoordinated movements and/or piloerection were noted for the animals between Days 1 and 3.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats conducted according to OECD 423 no mortality occurred at the limit dose of 2000 mg/kg bw. Hence, the LD50 value was determined to be greater than 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (acute toxic class method, OECD 423), six 8 weeks old, female Wistar rats were given a single oral dose of the test item (100.1% purity) in water at the limit dose of 2000 mg/kg bw and were observed for 14 days. All animals survived until the end of the study showing only mild signs of toxicity. The most relevant clinical findings were hunched posture, uncoordinated movements and/or piloerection between days 1 and 3. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal. Based on the results from this study, the oral LD50 in rats is considered to exceed 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study (acute toxic class method, OECD 423), six 8 weeks old, female Wistar rats were given a single oral dose of the test item (100.1% purity) in water at the limit dose of 2000 mg/kg bw and were observed for 14 days. All animals survived until the end of the study showing only mild signs of toxicity. The most relevant clinical findings were hunched posture, uncoordinated movements and/or piloerection between days 1 and 3. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal. Based on the results from this study, the oral LD50 in rats is considered to exceed 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, L-Histidine Hydrochloride Monohydrate (HHM) does not warrant classification for acute toxicity. The LD50 value for the oral route was above the limit value for classification (2000 mg/kg bw).