Ammonium carbamate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from handbook or collection of Data (peer reviewed, OECD SIDS)

Data source

Reference

Reference Type:

secondary source

Title:

Salicylate intoxication and congenital anomalies.

Author:

Goldman, A.S. and Yakovac, W.C.

Year:

1964

Bibliographic source:

Arch. Environ. Health. 8, 648-656 (1964), cited in: OECD SIDS Ammonium Chloride, Final 8/2006

Materials and methods

Principles of method if other than guideline:

The test substance is administered as a single dose to a group of 10 pregnant experimental Sprague Dawley rats for 4 days of pregnancy (from day 7-10) covering part of the period of organogenesis. Shortly before the expected date of delivery, the mother is sacrificed, the uterus removed, and the contents examined for embryonic or foetal deaths, and live foetuses.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium chloride

EC Number:

235-186-4

EC Name:

Ammonium chloride

Cas Number:

12125-02-9

Molecular formula:

ClH4N

IUPAC Name:

ammonium chloride

Details on test material:

- Name of test material (as cited in study report): Ammonium chloride
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

no data

Duration of treatment / exposure:

day 7 - 10 of gestation (4 days)

Frequency of treatment:

once a day

Duration of test:

20 days

Doses / concentrations

Dose / conc.:

8.9 mg/kg bw/day

Remarks:

1/6M, 1 ml/kg b.w. (equivalent to 8.9 mg/kg bw/day)

No. of animals per sex per dose:

10 female animals

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

Maternal death was inspected.

Fetal examinations:

The foetuses were examined grossly after delivery by cesarean section on day 20. Resorptions (early, late), number of conceptions, anomalous live young, growth-weight and height was inspected.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Acidosis was reported in the maternal animals treated with the test substance

Control /NH4Cl /Na salicylate (500mg/kg)
Maternal death(%): 0 /0 /0
No.of conceptions: 136 /122 /288

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

< 8.9 mg/kg bw/day (nominal)

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Control /NH4Cl /Na salicylate(500mg/kg)

Resorption-early(%): 6 /15 /15
Resorption-late(%) : 0 /1 /11
Anomalous live young(%): 0 /0 /14
Growth weight(g): 3.2 /2.0 /2.0
Growth height(mm):38 /27 /27

The effects of this substance on foetal survival and growth were considered a consequence of maternal acidosis by the authors. They argued that "The amount of 2.5 mEq/24 hours ammonium chloride consumed by pregnant rat in the study is sufficient to cause metabolic acidosis rats weighing between 250 and 300 g. Although, no statistical and/or background data were shown, it is agreeable. No foetus with malformations was observed in this substance-treated group. This substance has no teratogenicity at this dose level.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

< 8.9 mg/kg bw/day (nominal)

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

The authors regarded the decrements in foetuses length and weight as meaningfull findings, but considered them a corollary of maternal effects. The author referred to these effects as "the inhibition of growth by a metabolic acidosis".