Pyridinium, 2,6-dihydroxy-4-methyl-1-[3-(methylamino)propyl]-, sulfate (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dihydroxy-4-methyl-1-[3-(methylazaniumyl)propyl]pyridin-1-ium sulfate

EC Number:

931-673-7

Cas Number:

1333469-72-9

Molecular formula:

C10 H18 N2 O6 S1

IUPAC Name:

2,6-dihydroxy-4-methyl-1-[3-(methylazaniumyl)propyl]pyridin-1-ium sulfate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Rationale for use of males (if applicable): not specified
- Age at study initiation: 5 to 8 weeks old
- Weight at study initiation: males 139- 55g, females 124-149g
- Fasting period before study: no
- Housing: in groups of five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet and water: With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups: only selection at random is specified in the report

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21ºC
- Humidity (%): 37-60%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: range-finding study (1 male, 1 female)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

dose range-finding study: 1 male, 1 female
main study: 5 males, 5 females

Control animals:

no

Details on study design:

1) Range-finding study
A range-finding study was performed to determine a dosing regime as follows:
dose level (mg/kg): 2000
specific gravity: 1.326
dose volume: 1.51
1 male/ 1 female

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

2) Main study
Based on the results of the range-finding study a further group of animals was treated as follows:
dose level (mg/kg): 2000
specific gravity: 1.326
dose volume: 1.51
5 male/ 5 female

All animals were dosed once only in a similar manner to that used in the range-finding study.
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:

Individual clinical observations and mortality data are given in Table 1.

There were no deaths. Lethargy was noted.

The results of the range-finding study indicated that the acute oral median lethal dose of the test material was greater than 2000 mg/kg bodyweight.

Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Individual bodyweights, together with weekly bodyweight gain are given in Table 3. All animals showed expected gain in bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

HYMAP: RANGE-FINDING ACUTE ORAL TOXICITY TEST IN THE RAT

Table 1. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN THE RANGE-FINDING STUDY

 

Dose level Mg/kg	Animal number & sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		1/2	1	2	4	1	2	3	4	5
2000	1-0 Male	L	L	L	L	L	L	0	0	0
	2-0 Female	0	0	0	L	L	0	0	0	0

0= no signs of systemic toxicity; L= lethargy

Table 2. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN THE MAIN STUDY

Dose level Mg/kg	Animal number & sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	3-0 male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-4 male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-1 female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-4 female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0= no signs of systemic toxicity;

Table 3. INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT GAIN IN THE MAIN STUDY

Dose level mg/kg	Animal number & sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
2000	3-0 male	150	221	304	71	83
	3-1 male	148	181	241	33	60
	3-2 male	147	217	290	70	73
	3-3 male	139	204	274	65	70
	3-4 male	155	229	300	74	71
	4-0 female	124	147	181	23	34
	4-1 female	144	170	189	26	19
	4-2 female	129	171	202	42	31
	4-3 female	149	161	211	12	50
	4-4 female	146	173	206	27	33

Table 4: INDIVIDUAL NECROPSY FINDINGS IN THE MAIN STUDY

 

Dose level mg/kg	Animal number & sex
		Time of death	Macroscopic observations
2000	3-0 male	Killed day 14	No abnormalities detected
	3-1 male	Killed day 14	No abnormalities detected
	3-2 male	Killed day 14	No abnormalities detected
	3-3 male	Killed day 14	No abnormalities detected
	3-4 male	Killed day 14	No abnormalities detected
	4-0 female	Killed day 14	No abnormalities detected
	4-1 female	Killed day 14	No abnormalities detected
	4-2 female	Killed day 14	No abnormalities detected
	4-3 female	Killed day 14	No abnormalities detected
	4-4 female	Killed day 14	No abnormalities detected

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material, HYMAP, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight. The substance is not classified for acute oral toxicity according to CLP Regulation.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 401 "Acute Oral Toxicity" referenced as Method B1 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 91/325/EEC).

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material at a dose level of 2000 mg/kg. The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study.

All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg body-weigth. No symbol and risk phrase are required according to EEC labelling regulations.