Sodium azide

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

Based on the available repeat-dose studies and data from multiple available literature sources, there is no evidence of adverse effects on reproductive organs or tissues or reveal other concerns in relation with reproductive toxicity (see IUCLID chapter 7.5 Repeated dose toxicity). In addition, according to REACH Annex VIII column 2 a screening test for reproductive toxicity is not necessary for this tonnage band, if data is available from prenatal developmental toxicity or multi-generation studies.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A number of studies were located that examined the effect sodium azide has on the reproduction and embryo-fetal development in experimental animals.

 

A 2-year oral gavage study was undertaken in rats in which a number of reproductive organs (ovary, testis, epididymis, seminal vesicle and uterus) were examined using histological techniques (NTP, 1991). No treatment related adverse effects were reported in these tissues studies under haematoxylin and eosin staining. The male reproductive organs were studies in detail, with the epididymis being examined for spermatocele. The seminal vesicle was examined for atrophy and inflammation. The testes was examined for hypospermia, inflammation of the arteriole and interstitial cell hyperplasia. No adverse effects were reported in any of these tissues when compared with the same tissues from control animals. This study gives a good indication that long-term treatment with sodium azide did not cause any changes to the morphology of the reproductive organs of experimental animals.

The NTP study reports of a study in rats in which there were no changes to the oestrous cycle following 1 -year treatment via the oral route (unspecified) of administration with sodium azide at concentrations up to 5 mg/kg bw/day (reference held on-line at NIEHS - cited in NTP, 1991). No further details about this study were available for review.

A study by Faqi (2008) where dams treated with sodium azide by oral gavage showed that maternal deaths occurred at the top dose only. No deaths or clinical signs of toxicity or body weight effects were reported at the other doses. No histopathological investigations were reported to have been undertaken in this study. The pregnancy index in this study was 100% in the treated animals, which was comparable with the controls at 96%. This indicates that the administration of sodium azide to pregnant animals did not modify the ability of the dams to deliver pups. Although clinical toxicity was observed at the top dose no other adverse effects were observed at the other doses to the dams.

 

Effects on developmental toxicity

Description of key information

 

The effects of sodium azide on the embryo-fetal development in rats showed that fetal weights were decreased in the pups at the top dose (Faqi, 2008). No other adverse effects on the embryo-fetal development were reported. The decrease in fetal weight coincided with maternal signs of clinical toxicity that included decreased activity, prostration, loss of righting reflex, lacrimation, impaired limb function, swelling (head and face), moribundity, difficult/slow/shallow breathing, and mortality. The authors state that this decrease in fetal weight could be the result of dams decreasing food intake as a result of the clinical signs toxicity. This study clearly shows that embryo-fetal toxicity occurs only at doses that are toxic to the dams and, due to the lack of an adverse effect at the other doses, shows that sodium azide does not have an effect on the development of the fetuses.

 

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Sodium azide
- Analytical purity: no data
- Impurities (identity and concentrations): no data

Species:

rat

Strain:

Crj: CD(SD)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan, USA
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 208-210 g mean body weight
- Fasting period before study:
- Housing: individually in suspended, stainless steel, wire-mash type cages in an environmentally controlled room.
- Diet (e.g. ad libitum): Lab Diet Certified Rodent Diet #5002, PMI Nutrition International Inc., ad libitum
- Water (e.g. ad libitum): no data
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26 °C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: distilled water, buffered to pH 9.5 with NaOH

Details on exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water): not given
- Concentration in vehicle: 0 mg/kg
- Amount of vehicle (if gavage): 5 mL/kg bw

Analytical verification of doses or concentrations:

no

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant

Duration of treatment / exposure:

Control and test article administration began on GD 6 and continued to include GD 19 for all animals. The test article was administered to the treated groups by oral gavage once per day at approximately the same time each day at dosage levels of 1, 5, and 17.5 mg/kg/bw/day at a dosage volume of 5 mL/kg based on the body weight. From GD 10-12, surviving animals at 17.5 mg/kg bw/day began receiving a reduced dosage level of 10 mg/kg bw/day at a dosage volume of 2.86 mL/kg.
The control animals received the vehicle, distilled water (buffered at pH 9.5 with sodium hydroxide), at a volume of 5 mL/kg and dosing regimen as the treated animals.

Frequency of treatment:

once a day

Duration of test:

gestation day (GD) 6 to 19: 13 days

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

control

Dose / conc.:

1 mg/kg bw/day (nominal)

Remarks:

low dose

Dose / conc.:

5 mg/kg bw/day (nominal)

Remarks:

mid dose

Dose / conc.:

17.5 mg/kg bw/day (nominal)

Remarks:

high dose

No. of animals per sex per dose:

25

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The highest dose was selected based on 90-day oral gavage study in rats (NCI, 1981). In this study nearly total mortality occurred at the 20 mg/kg dose over the experimental period, but no deaths occurred at other doses including 10 mg/kg bw/day. Of the total females in the study, two females died in each week 2, and 6 and six females died on Week 7 of the study. In males the death occurred between weeks 7 and 13 of the study. As the mortality effect observed at 20 mg/kg bw/day in the NCI (1981) study was over a longer period, and while the duration of the current study was only 14 days; it was decided that a 17.5 mg/kg bw/day would be appropriate for use as the highest dose in this study. Then, the high-dose (17.5 mg/kg bw/day) was reduced to 10 mg/kg/day due to severe maternal mortality.

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: not given


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not given


BODY WEIGHT: Yes
- Time schedule for examinations: not given


FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: complete necropsy including uterine examination

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: Number of live and dead fetuses

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: No data
- Skeletal examinations: Yes: [half per litter]
- Head examinations: No
- Visceral examinations: Yes: [half per litter]

Statistics:

Mean and SDs were calculated for all measured parameters. Gestation body weights, gestation body weight gains, and gestation food consumption were analyzed by ANOVA followed, where appropriate, by Dunnett's test. Comparison of litter (fetal) body weight data was analyzed by ANOVA; the litter was the unit of observation. For reproductive parameters, a one factor (i.e. treatment group) ANOVA was used for mean corpora lutea, mean total, live and non-live (resorptions and death) implants, mean percent live and non-live implants, and mean percent preand post implantation loss. Visceral and skeletal data were analyzed by Fisher's Exact Test. Sex ratio (% male/litter) was transformed using Arcsin square-root transformation. The transformed data was then analyzed using Dunnett's adjusted t-test and or Welch's f-test with a Bonferroni correction as appropriate. A minimum significance level of p = 0.05 was used for all comparisons.

Indices:

no data

Historical control data:

The mean values of implantation sites and mean viable fetuses at 17.5/10 mg/kg bw/day were within the laboratory's historical background of the species of rats used in the study.
No data on comparison of other treatment groups to historical controls are made.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

For more details see "details on results" section below.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

For more details see "details on results" section below.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

For more details see "details on results" section below.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

For more details see "details on results" section below.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Endocrine findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not examined

Details on results:

A total of 20 out of 25 dams in the high-dose group (17.5 mg/kg bw/day) died between GD 8 and GD 10. From GD 10-12, the dosage level for the surviving animals (n = 5) was then reduced to 10 mg/kg bw/day. Two out of the 5 surviving animals died after the dose was reduced to 10 mg/kg bw/day. All the animals died between GD 8 and GD 12 of the study. No death was observed in the low- (1 mg/kg bw/day) and mid-dose group (5 mg/kg bw/day).
Treatment-related clinical signs of toxicity were observed in the high-dose group (17.5/10 mg/kg bw/day), which included decreased activity, prostration, loss of righting reflex, lacrimation, impaired limb function, swelling (head and face), moribundity, and difficult/slow/shallow breathing. Although the mortality was sodium azide induced, no sodium azide-related macroscopic lesions were observed in dams at necropsy.
Gestation body weight and gestation body weight changes were significantly decreased in the animals receiving the high-dose (17.5/10 mg/kg bw/day; Tables 1 and 2) when compared to the control animals. Gestation body weight and gestation body weight changes were not affected in the animals receiving 1 and 5 mg/kg bw/day. Similarly, gestation food consumption was significantly impacted in the animals of the high-dose group (Table 3). Corrected final GD 20 body weight and corrected weight change (GD 0-20) were significantly decreased at 17.5/10 mg/kg bw/day in comparison to the control animals.

Number of abortions:

no effects observed

Pre- and post-implantation loss:

effects observed, non-treatment-related

Description (incidence and severity):

For more details see "details on maternal toxic effects" section below.

Total litter losses by resorption:

not specified

Early or late resorptions:

no effects observed

Dead fetuses:

effects observed, treatment-related

Description (incidence and severity):

For more details see "details on maternal toxic effects" section below.

Changes in pregnancy duration:

not specified

Changes in number of pregnant:

no effects observed

Details on maternal toxic effects:

The pregnancy index was 96% in the control and 100% in the treatment groups. A total of 22 animals died at 17.5/10 mg/kg bw/day. Resultant number of dams with viable fetuses at GD 20 was 24, 25, 25, and 3 in the control, 1 mg/kg bw/day, 5 mg/kg bw/day, and 17.5 /10 mg/kg bw/day groups, respectively. Implantation sites, viable fetuses, and litter size per dam were significantly higher in the high-dose group (17.5/10 mg/kg bw/day) in comparison to the control group. This was not considered to be sodium azide-related, as comparison to the control is difficult due to the small number of surviving dams (n = 3) available on GD 20 for this group. All the other uterine parameters examined during the study were comparable among the groups.

Dose descriptor:

NOAEL

Effect level:

5 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Dose descriptor:

LOAEL

Effect level:

17.5 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Remarks on result:

other: At days 10-12, high-dose (17.5 mg/kg bw/day) was reduced to 10 mg/kg/day due to severe maternal mortality

Abnormalities:

no effects observed

Fetal body weight changes:

effects observed, treatment-related

Description (incidence and severity):

For more details see "details on embryotoxic/teratogenic effects" section below.

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

no effects observed

Anogenital distance of all rodent fetuses:

not examined

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Details on embryotoxic / teratogenic effects:

Fetal body weights were significantly affected in the three remaining litters at 17.5/10 mg/kg bw/day.However, no effects of treatment were evident from fetal external, visceral or skeletal examinations at any of the dose levels evaluated.

Dose descriptor:

NOAEL

Effect level:

5 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Dose descriptor:

LOAEL

Effect level:

17.5 mg/kg bw/day (nominal)

Basis for effect level:

fetal/pup body weight changes

Remarks on result:

other: At days 10-12, high-dose (17.5 mg/kg bw/day) was reduced to 10 mg/kg/day due to severe maternal mortality

Abnormalities:

no effects observed

Developmental effects observed:

no

Table 1: Gestation body weight (g)

Gestation days	Control	1 mg/kg bw/day	5 mg/kg bw/day	17.5 mg/kg bw/day
0	207.9 ± 13.5 (n = 24)	208.9 ± 10.7 (n =25)	210.5 ± 11.8 (n =25)	209.6 ± 11.8 (n = 25)
6	250.0 ± 15.8 (n = 24)	248.3 ± 12.5 (n = 25)	249.5 ± 13.1 (n = 25)	249.6 ± 14.3 (n = 25)
9	266.3 ± 18.0 (n = 24)	262.7 ± 13.5 (n = 25)	265.6 ± 14.1 (n = 25)	247.8 ± 17.4** (n = 20)
12	282.8 ± 12.3 (n = 24)	280.3 ± 15.7 (n = 25)	282.8 ± 13.7 (n = 25)	219.1 ± 32.6** (n = 4)
15	301 ± 22.5 (n = 24)	301.4 ± 18.1 (n = 25)	302.7 ± 15.7 (n = 25)	248.7 ± 39.1** (n = 3)
18	338.7 ± 25.2 (n = 24)	337.6 ± 25.2 (n = 25)	339.8 ± 18.1 (n = 25)	295.1 ± 53.7* (n = 3)
20	371.6 ± 27.2 (n = 24)	370.6 ± 27.7 (n = 25)	374.2 ± 20.2 (n = 25)	326.5 ±42.1* (n = 3)

Note: Data are means ± SD; from GD 10-12, the high-dose was reduced to 10 mg/kg bw/day;
n = corresponds to the number of animals.

* Significantly different from control (p < 0.05)

** Significantly different from control (p < 0.01)

 

Table 2: Gestation body weight gain (g)

Gestation interval (days)	Control	1 mg/kg bw/day	5 mg/kg bw/day	17.5 mg/kg bw/day
0-6	42.1 ± 6.5 (n = 25)	39.3 ± 7.9 (n = 25)	39.0 ± 5.8 (n = 25)	40.1 ± 6.2 (n = 25)
6-9	16.3 ± 5.6 (n = 24)	14.4 ± 4.9 (n = 25)	16.1 ± 6.0 (n =25)	-1.6 ± 11.4** (n =25)
9-12	16.59 ± 5.2 (n =24)	17.6 ± 6.5 (n = 25)	17.2 ± 4.0 (n =25)	-27.0 ± 15.2** (n = 20)
12-15	18.2 ± 7.8 (n = 24)	21.1 ± 5.7 (n = 25)	19.9 ± 5.5 (n =25)	16.6± 15.9 (n = 4)
15-18	37.7 ± 7.9 (n = 24)	36.2 ± 10.4 (n = 25)	37.0 ± 6.6 (n =25)	46.4 ± 15.4 (n = 3)
18-20	32.9 ± 6.5 (n = 24)	33.0 ± 5.2 (n = 25)	34.4 ± 5.2 (n =25)	31.4± 12.3 (n = 3)
6-20	121.6 ± 16.8 (n =24)	122.3 ± 19.7 (n = 25)	124.7 ± 16.4 (n =25)	79.8 ± 15.7** (n = 3)
0-20	163.7 ± 19.5 (n = 24)	161.6 ±23.7 (n = 25)	163.7 ± 17.0 (n =25)	122.0 ± 17.9** (n = 3)

Note: Data are means ± SD; from GD 10-12, the high-dose was reduced to 10 mg/kg bw/day;
n = corresponds to the number of animals.

** Significantly different from control (p < 0.01)

 

Table 3: Gestation food consumption (g)

Gestation interval (days)	Control	1 mg/kg bw/day	5 mg/kg bw/day	17.5 mg/kg bw/day
0-6	19.9 ± 3.0 (n = 24)	20.7 ± 1.8 (n = 25)	21.0 ± 2.4 (n = 25)	20.7 ± 1.5 (n = 25)
6-9	23.6 ± 2.8 (n = 24)	22.8 ± 2.1 (n = 25)	22.6 ± 3.3 (n = 25)	15.7 ± 5.9** (n = 20)
9-12	24.4 ± 2.2 (n = 24)	24.0 ± 2.4 (n= 25)	24.6 ± 1.9 (n = 25)	9.1 ± 4.4** (n = 4)
12-15	25.1 ± 3.5 (n = 24)	26.1 ± 2.5 (n – 25)	25.5 ± 3.4 (n = 25)	14.7 ± 4.2** (n - 3)
15-18	27.9 ± 2.8 (n = 24)	27.5 ± 3.6 (n - 25)	27.5 ± 2.8 (n = 25)	23.6 ± 5.7 (n = 3)
18-20	28.6 ± 3.9 (n = 24)	27.9 ± 3.2 (n = 25)	28.3 ± 2.4 (n = 25)	26.2 ± 0.8 (n = 3)
6-20	25.7 ± 2.1 (n = 24)	25.5 ± 2.5 (n = 25)	25.6 ± 2.1 (n = 25)	17.9 ± 1.9** (n = 3)
0-20	23.9 ± 2.1 (n = 24)	24.0 ± 2.2 (n =25)	24.3 ± 2.0 (n = 25)	18.3 ± 1.0** (n = 3)

Note: Data are means ± SD; from GD 10-12, the high-dose was reduced to 10 mg/kg bw/day;
n = corresponds to the number of animals.

** Significantly different from control (p < 0.01)

 

Table 4: Summary of maternal and uterine data

Endpoints	Control	1 mg/kg bw/day	5 mg/kg bw/day	17.5 mg/kg bw/day
No. females on study	25	25	25	25
Number pregnant	24	25	25	25
Number not pregnant	1	0	0	0
Pregnancy index (%)	96	100	100	100
Number died pregnant	0	0	0	22
Number females with viable fetuses	24	25	25	3
Number of corpora lutea/animal	13.0 ± 1.85 (n = 24)	13.6 ± 1.82 (n = 25)	13.9 ± 1.87 (n = 25)	13.9 ± 1.87 (n = 3)
Implantation sites per animal	12.2 ± 1.55 (n = 24)	12.6 ± 1.58 (n = 25)	13.1 ±2.31 (n = 25)	15.0 ± 1.73* (n = 3)
Pre-implantation loss per animal	10.84 ± 10.460 (n = 24)	7.49 ± 7.897 (n = 25)	5.87 ± 12.795 (n = 25)	4.07 ± 3.572 (n = 3)
Viable fetuses per animal	11.7 ± 1.65 (n = 24)	12.0 ± 1.70 (n =25)	12.8 ± 2.38 (n = 25)	14.7 ± 2.08* (n = 3)
Post-implantation loss (% implants per animal)	3.77 ± 5.728 (n = 24)	4.11 ±6.499 (n = 25)	2.22 ± 3.710 (n =25)	2.38 ± 4.124 (n =3)
Nonviable fetuses/animal	0.0 ± 0.0 (n = 24)	0.0 ± 0.0 (n = 25)	0.0 ± 0.0 (n = 25)	0.0 ± 0.0 (n = 3)
Resorptions (early + late)	0.5 ± 0.7 (n = 24)	0.5 ± 0.8 (n = 25)	0.3 ± 0.5 (n =25)	0.3 ± 0.6 (n = 3)
Fetal weight (g)
Male (M)	4.08 ± 0.250 (n = 24)	4.13 ± 0.286 (n = 25)	4.10 ± 0.293 (n = 25)	3.57 ± 0.269 (n = 3)
Female (F)	3.89 ± 0.263 (n =24)	3.88 ± 0.289 (n = 25)	3.88 ± 0.245 (n = 25)	3.36 ± 0.224* (n = 3)
Combined (M + F)	3.89 ± 0.263 (n = 24)	4.01 ± 0.273 (n = 25)	4.00 ± 0.251 (n = 25)	3.44 ± 0.203* (n = 3)
Sex ratio (mean % of males/litter)	50.8 ± 15.8 (n = 24)	55.8 ± 15.7 (n = 25)	44.8 ± 12.3 (n = 25)	45.4 ± 24.2 (n = 3)

Note: Data are means ± SD
n = corresponds to the number of litters examined; from GD 10-12, the high-dose was reduced to 10 mg/kg bw/day.

* Significantly different from control (p < 0.05).

Conclusions:

Overt maternal and developmental toxicity was observed at a dosage level of 17.5/10 mg/kg bw/day, which can be considered as LOAEL. No adverse effects were observed in the lower dose groups and therefore the NOAEL is considered to be 5 mg/kg bw/day. The decrease in fetal weight at the highest dose coincided with maternal signs of clinical toxicity, therefore sodium azide does not have an effect on the development of the fetuses.

Executive summary:

In a developmental toxicity study (equivalent to OECD Guideline 414) sodium azide was administered to 25 sperm-positive SD rats/dose by gavageat dose levels of 0, 1, 5, or 17.5 mg/kg bw/day from days 6 through 19 of gestation (GD). From GD 10 -12, the high-dose was reduced to 10 mg/kg bw/day due to maternal mortality. Cesarean section was performed on GD 20 and implantation and resorption sites, live and dead fetuses were counted. Fetuses were weighed, sexed externally and processed for gross external, visceral and skeletal examinations. A high rate of maternal mortality; reduced gestation body weight, gestation body weight changes and food consumption; decreased corrected body weight and corrected weight gain were observed at 17.5/10 mg/kg bw/day. Fetal weight was also reduced at 17.5/10 mg/kg bw/day. There were no maternal deaths, clinical signs or body weight effects that were considered related to sodium azide at 1 and 5 mg/kg bw/day. No increase in the incidence of malformations and variations were observed at any of the doses evaluated. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) and the Lowest Observed Adverse Effect Level (LOAEL) for maternal and developmental toxicity of sodium azide in rats were considered to be 5 and 10 mg/kg bw/day, respectively. The decrease in fetal weight coincided with maternal signs of clinical toxicity that included decreased activity, prostration, loss of righting reflex, lacrimation, impaired limb function, swelling (head and face), moribundity, difficult/slow/shallow breathing, and mortality. The decrease in fetal weight could be the result of dams decreasing food intake as a result of the clinical signs toxicity. This study clearly shows that embryo-fetal toxicity occurs only at doses that are toxic to the dams and, due to the lack of an adverse effect at the other doses, shows that sodium azide does not have an effect on the development of the fetuses.

 

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

5 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

comparable to guideline study with acceptable restrictions

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In a study to determine the maternal and developmental toxicity of sodium azide in rats, sperm-positive Sprague-Dawley rats were treated with sodium azide via oral gavage once daily from Gestation Day (GD) 6 through 19 at respective dose levels of 0, 1, 5, and 17.5 mg/kg bw/day. From GD 10-12, the high-dose was reduced to 10 mg/kg bw/day due to maternal mortality. The embryo-fetal toxicity occured only at doses that are toxic to the dams and, due to the lack of an adverse effect at the other doses, shows that sodium azide does not have an effect on the development of the fetuses (Faqi 2008).

 

Pairs of osmotic minipumps containing 400 mg/mL (6.15 M) sodium azide in distilled water were subcutaneously implanted in timed pregnancy Syrian golden hamsters. The total delivered dose was calculated as 60 µmol/kg/hr at the maximal pumping rate. The test chemical was administered by continuous subcutaneous infusion over two days during GD 7 to 9. The adverse effects, as evidenced by fetal resorptions, was seen at the top dose, which coincided with maternal toxicity. However, the number of malformations (in the form of encephaloceles) was not statistically significant at the top dose. The decrease in fetus/litter size at the top dose was also not statistically significant. Sodium azide is not considered to be teratogenic in hamsters, and it produces embryotoxicity only at dose rates that result in toxic signs in the dams (Sana 1990).

 

Toxicity to reproduction: other studies

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The objective of this study was to determine the toxicity potential of sodium azide on muse embryo development in vitro.

GLP compliance:

no

Type of method:

in vitro

Species:

mouse

Strain:

not specified

Details on test animals or test system and environmental conditions:

Pronuclear mouse embryos

Conclusions:

Sodium azide has a drastically toxic effect on the in vitro growth of mouse embryos at concentrations of 10^(-4) mol/L in the petri dish or greater.

Executive summary:

The toxicity potential of sodium azide on mouse development was determined in vitro. Embryos were treated with sodium azide and evaluated following 72 hours of culture. The results show that sodium azide has a drastically toxic effect on the in vitro growth of mouse embryos at concentrations of 10 -4 mol/L in the petri dish or greater. It was toxic to most, though not all, mouse embryos at 10 -5 mol/L but was not significantly toxic at levels of 10 -6 mol/L or less.

The study does not follow any guideline and is not GLP compliant. Moreover, further details are not available for this study and documentaion is insufficient for assessment.

 

Additional information

In a study conducted by Robertson J.L. and Roudebush W.E., the toxicity potential of sodium azide was determined in vitro. Embryos were treated with sodium azide and evaluated following 72 hours of culture. The study reports toxic effects of sodium azide on the in vitro growth of mouse embryos at concentrations of 10^(-4) mol/L in the petri dish or greater. The study does not follow any guideline and is not GLP compliant. Moreover, further details are not available for this study and documentaion is insufficient for assessment.

 

Justification for classification or non-classification

Based on the results from a number of repeated dose and developmental toxicity studies, there is no evidence of adverse effects on reproductive organs or tissues or of other concerns in relation with reproductive and developmental toxicity. Although embryotoxicity has been reported, this was only observed in association with maternal toxicity and can be considered a secondary effect. Therefore, no classification for developmental/reproductive toxicity is warranted for sodium azide.