Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Remarks:

Organ toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from HSDB

Data source

Reference

Reference 1

Reference Type:

other: authoritative database

Title:

Subchronic toxicity study for Ametryne in Rat

Author:

U. S. National Library of Medicine

Year:

2017

Bibliographic source:

HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2017

Reference 2

Reference Type:

secondary source

Title:

Health Advisories for 50 Pesticides (Ametryn)

Author:

Environmental Protection Agency

Year:

1988

Bibliographic source:

NTRL (National Technical Reports Library), Environmental Protection Agency, 1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Subchronic toxicity study of Ametryne in rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ametryn

EC Number:

212-634-7

EC Name:

Ametryn

Cas Number:

834-12-8

Molecular formula:

C9H17N5S

IUPAC Name:

2-ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine

Details on test material:

- Name of test material (as cited in study report): Ametryne (2-ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine)
- Molecular formula (if other than submission substance): C9H17N5S
- Molecular weight (if other than submission substance): 227.3343 g/mole
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material (as cited in study report): Ametryne (2-ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine)
- Molecular formula (if other than submission substance): C9H17N5S
- Molecular weight (if other than submission substance): 227.3343 g/mole
- Substance type: Organic

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Details on exposure:

not specified

Details on mating procedure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28-day

Frequency of treatment:

6 days/week

Details on study schedule:

not specified

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

250 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

500 mg/kg bw/day

No. of animals per sex per dose:

Total: 40
0 mg/kg/day: 5 male, 5 female
100 mg/kg/day: 5 male, 5 female
250 mg/kg/day: 5 male, 5 female
500 mg/kg/day: 5 male, 5 female

Control animals:

yes

Details on study design:

not specified

Positive control:

not specified

Examinations

Parental animals: Observations and examinations:

Survival, Clinical sign and Body weight were examined.

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

Gross pathology and histopathology were examined.

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Emaciated animals were observed at 500 mg/kg bw.

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

When treated with 500 mg/kg bw, 7 animals died out of 10.
When treated with 250 mg/kg bw, 1 animals died out of 10.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

When treated with 250 and 500 mg/kg bw, decrease in body weight gain were observed in treated rats.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

When treated with 500 mg/kg bw, severe vascular congestion, centrilobular liver necrosis and fatty degeneration of individual liver cells were observed in treated rats.

When treated with 250 mg/kg bw, no major degenerative changes were observed in liver, kidney, spleen, pancreas, heart, lung, intestine and gonads of treated

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

clinical signs

mortality

body weight and weight gain

histopathology: non-neoplastic

other: No effect on Histopathology of repeoductive organ

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Effect levels (F1)

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Target system / organ toxicity (F1)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Results: F2 generation

Effect levels (F2)

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Target system / organ toxicity (F2)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 250 mg/kg/day for P generation when male and female rats treated with Ametryne orally by gavage for 28 days.

Executive summary:

In a Subchronic toxicity study,male and female rat were treated with Ametrynein the concentration of 0, 100, 250 and 500 mg/kg/day orally by gavage for 28 days. 7 animals died out of 10 at 500 mg/kg bw and 1 animals died out of 10 at 250 mg/kg bw. Decrease in body weight gain were observed in treated rats at 250 and 500 mg/kg bw. Similarly, severe vascular congestion, centrilobular liver necrosis and fatty degeneration of individual liver cells were observed in treated rats at 500 mg/kg bw. In addition, no major degenerative changes were observed in liver, kidney, spleen, pancreas, heart, lung, intestine and gonads of treated rats at 250 mg/kg bw. Therefore, NOAEL was considered to be 250 mg/kg/day for P generation when male and female rats treated with Ametryne orally by gavage for 28 days.