4-[2-[4-[benzylmethyl(ethyl)amino]phenyl]vinyl]-1-(2-hydroxyethyl)pyridinium acetate

Endpoint summary

Description of key information

Rats (5/sex/dose) received a single dose of the substance by gavage ( 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg). Mortality (within 4 hours after dosing) was 0, 0, 3, 4 ,9 and 10 at 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg. During the 14 day observation period diarrhea, nausea, sedation and convulsions were observed in surviving animals. Necropsy of decedents was not possible due to orange discoloration of the organs. In survivors no abnormalities were recorded. The LD50 (as assessed by the author of the report) is 1700 mg/kg bw. No correction for purity was made as the composition of the tested substance is similar to that of the substance subject to registration (Bayer 1981)

In an acute dermal toxicity study (limit test) the LD50 of the substance is > 2000 mg/kg bw (Eurofins 2017). No signs of toxicity were observed.

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:

October-November 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

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: Winkelmann Borchen Germany
- Strain: Wistar TNO/W
- Age at study initiation: males 9 weeks. females 14 weeks
- Weight at study initiation: males 157-185 g, females 151-176 g
- Fasting period before study: yes 16 hours pre-dosing and 4 hours post-dosing
- Housing: 5/sex in Macrolon type III cages
- Diet: Altromin R3 1324 (Altromin GmbH Lage, Germany) ad libitum
- Water: tap water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 60 °C 5 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

0.31, 1.0, 1.25, 1.6, 2.5 and 5.0 mL/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: clinical signs and mortality twice daily
- Body weight: on day 0, 7 and 14
- Necropsy: on all animals

Statistics:

probit analyses

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1.56 mL/kg bw

Based on:

test mat.

95% CL:

>= 1.38 - <= 1.8

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 700 mg/kg bw

Based on:

test mat.

Mortality:

males: 0, 0, 1, 1 ,4 and 5 at 0.31, 1.0, 1.25, 1.6 2.5 and 5.0 mL/kg
females: 0, 0, 2, 3, 5 and 5 at 0.31, 1.0, 1.25, 1.6 2.5 and 5.0 mL/kg
Mortality was within 4 hours after dosing

Clinical signs:

at 1.0 mg/L: nausea in one male and one female
at 1.25 mg/L: diarrhea, nausea and sedation in all animals
at 1.6 and above: diarrhea, nausea, sedation and convulsions in all animals

Body weight:

no data

Gross pathology:

In decedents: orange discoloration prevented examination
in survivors: no findings

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 in rats is 1700 mg/kg bw

Executive summary:

Rats (5/sex/dose) received a single dose of the substance by gavage ( 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg). Mortality (within 4 hours after dosing) was 0, 0, 3, 4 ,9 and 10 at 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg. During the 14 day observation period diarrhea, nausea, sedation and convulsions were observed in surviving animals. Necropsy of decedents was not possible due to orange discoloration of the organs. In survivors no abnormalities were recorded. The LD50 (as assessed by the author of the report) is 1700 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 700 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:

experimental study

Adequacy of study:

key study

Study period:

04 September 2017 to 26 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Strain: WISTAR rats Crl: WI(Han)
- Females (if applicable) nulliparous and non-pregnant:yes
- Age at study initiation: males 9-10 weeks; females 12-13 weeks
- Weight at study initiation: Males: 235g - 244g; Females 205g - 227g
- Fasting period before study: NA
- Housing: individually in in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: Altromin 1324 maintenance diet for rats and mice ad libitum
- Water: tap water, sulphur acidified to a pH value of approximately 2.8 ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of the body surface
- % coverage: 10% of the body surface
- Type of wrap if used: gauze-dressing and non-irritating tape and was fixed with an additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with aqua ad injectionem
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males + 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical signs and irritation (Draize): once within 30 min after dosing, several times upto 4 hours after dosing, daily thereafter
- Body weight: on day 1, 8 and 15
- Necropsy of survivors performed: yes macroscopic examination

Statistics:

NA

Key result

Sex:

male/female

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: irritation was observed

Mortality:

none

Clinical signs:

no systemic effects, red discoloration of the skin in all animals

Body weight:

within normal limits

Gross pathology:

no findings

Other findings:

A crust was observed in 3 of 5 male and 1 of 5 female animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the substance is > 2000 mg/kg bw

Executive summary:

LD₅₀:                                      > 2000 mg/kg bw

Species/strain:                      WISTAR Crl: WI(Han) rats

Vehicle (moistening):             no vehicle used

Number of animals:               5 male and 5 female

Duration of exposure:           24 hours

Method:                                OECD 402, EC 440/2008, Method B.3

Table1:  Results

Sex	Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths
male	2000	5	0
female	2000	5	0

bw = body weight

Signs of systemic toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

Effect on organs (related to dose level):

No treatment-related effects were observed.

Signs of irritation:

No erythema or oedema was observed. A crust was observed in 3 of 5 male and 1 of 5 female animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

Based on the available information, the substance needs to be classified as H302: Harmful if swallowed (acute tox cat 4) according to EC Regulation No 1272/2008 (CLP). No classification for acute dermal toxicity is considered necessary.