Skip to Main Navigation
Skip to Page Content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Share This:
https://ntp.niehs.nih.gov/go/gmm10abs

Abstract for GMM-10

Toxicology Study of Diispropylcarbodiimide in Genetically Modified (FVB Tg.AC Hemizygous) Mice and Carcinogenicity Study of Diispropylcarbodiimide in Genetically Modified [B6.129-Trp53tm1Brd (N5) Haploinsufficient] Mice (Dermal Studies)

CASRN: 693-13-0
Chemical Formula: C7H14N2
Molecular Weight: 126.20
Synonyms/Common Names: 1,3-Diisopropylcarbodiimide; N,N'-diisopropylcarbodiimide; N,N'-methanetetraylbis (2-propanamine)
Report Date: March 2007

FULL REPORT PDF

Abstract

Diisopropylcarbodiimide is used as a reagent for a variety of reactions including peptide syntheses. The National Cancer Institute nominated diisopropylcarbodiimide for study as a representative chemical in the alkylcarbodiimide class because of its acute toxicity, widespread low-level human exposure, and the absence of data on health effects. Female Tg.AC hemizygous or p53 haploinsufficient mice were administered diisopropylcarbodiimide (greater than 99% pure) dermally for 20 or 27 weeks, respectively.

20-Week Study in Tg.AC Hemizygous Mice

Groups of 10 female Tg.AC hemizygous mice received dermal applications of 0, 4.38, 8.75, 17.5, 35, or 70 mg diisopropylcarbodiimide/kg body weight in ethanol, 5 days a week for 20 weeks. Twelve animals died or were sacrificed moribund prior to the end of the study; two each from vehicle controls, 4.38, 8.75, and 17.5 mg/kg groups, and four from the 35 mg/kg group. Premature deaths were not associated with chemical-related lesions. Odontoma, a common spontaneous finding in Tg.AC hemizygous mice, resulting in jaw malformation, malocclusion, and loss of body condition, occurred in the majority of control, 4.38, 8.75, and 17.5 mg/kg animals that died prematurely. Of the surviving animals, mean body weights were similar to those of vehicle controls. There were no significant changes in organ weights and no treatment-related clinical findings. No neoplasms or nonneoplastic lesions were attributed to administration of diisopropylcarbodiimide.

27-Week Study in p53 Haploinsufficient Mice

Groups of 15 female p53 haploinsufficient mice received dermal applications of 0, 4.38, 8.75, 17.5, 35, or 70 mg/kg diisopropylcarbodiimide in ethanol, 5 days a week for 27 weeks. All animals survived to the end of the study. Mean body weights were similar to those of vehicle controls, and there were no treatment-related clinical findings. At necropsy there were no treatment-related gross lesions. Microscopically, there was a higher incidence of treatment-related, predominantly minimal epidermal hyperplasia at the site of application in 70 mg/kg mice than in vehicle controls. No neoplasms were attributed to the administration of diisopropylcarbodiimide.

Conclusions

Under the conditions of this 27-week study, there was no evidence of carcinogenic activity of diisopropylcarbodiimide in female p53 haploinsufficient mice administered 4.38, 8.75, 17.5, 35, or 70 mg/kg in ethanol.

There were no treatment-related neoplasms or nonneoplastic lesions in female Tg.AC hemizygous mice administered 4.38, 8.75, 17.5, 35, or 70 mg/kg in ethanol for 20 weeks.

Studies

Summary of the 20-Week Toxicology Study of Diisopropylcarbodiimide in Female Tg.AC Hemizygous Mice

Doses in ethanol by dermal application Vehicle control, 4.38, 8.75, 17.5, 35, and 70 mg/kg
 
Body weights Exposed groups similar to the vehicle control group
Survival rates 8/10, 8/10, 8/10, 8/10, 6/10, 10/10
Nonneoplastic effects None
Neoplastic effects None

Summary of the 27-Week Carcinogenesis Study of Diisopropylcarbodiimide in Female p53 Haploinsufficient Mice

Doses in ethanol by dermal application Vehicle control, 4.38, 8.75, 17.5, 35, and 70 mg/kg
 
Body weights Exposed groups similar to the vehicle control group
Survival rates 15/15, 15/15, 15/15, 15/15, 15/15, 15/15
Nonneoplastic effects Skin: epidermal hyperplasia (0/15, 0/15, 0/15, 0/15, 0/15, 8/15)
Neoplastic effects None
Level of evidence of carcinogenic activity No evidence